1. 1. Radiation of Head and Neck Tumors
Robert Kagan, MD,
Division of Radiation Oncology, Kaiser
Permanente
John Beumer III, DDS, MS
Division of Advanced Prosthodontics,
Biomaterials and Hospital Dentistry and the Jane
and Jerry Weintraub Center for Reconstructive
Biotechnology
UCLA School of Dentistry
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2. Radiation of Head and Neck Tumors
v Introduction Table of Contents
v Biologic effects
v Modalities
v Fractionation
v Methods
v CRT
v IMRT
v Brachytherapy
v ChemoRT
v Indications and key facts
v Tissue changes
v Immediate
v Long term

3. Radiation of Head and Neck Tumors
Introduction
Changes since the turn of the century
v Doseescalation particularly with post-operative radiation
therapy
v Postoperative
doses have increased from 50 Gy to 60 Gy and
sometimes accompanied by concomitant chemotherapy
v ChemoRT – Adds bio-equivalent of 7-10 Gy to the
irradiated tissues and impacts the tissues out of the
treatment volume as well.
" Post treatment morbidity dramatically increased!!
" Is immune surveillance compromised?
" Rate of development of second oral primaries and other cancers has
not yet been studied?
v IMRT
" Impact on salivary flow, the incidence of ORN,

4. Radiation of Head and Neck Tumors
Impact of these changes
v Preradiation dental screening
v Dose and volume of tissues receiving the highest
levels of dose will vary considerably from patient
to patient
v Acute side effects
v The use of ChemoRT dramatically increases the
acute side effects
v The use of IMRT probably decreases the acute
side effects

5. Radiation of Head and Neck Tumors
Impact of these changes
v Incidence of post treatment morbidity is rising
" Xerostomia – Probably not effected by IMRT
because the relatively low doses (26-40 Gy) will
severely damage the salivary gland parenchyma.
" Mucosal atrophy
" Caries
" Dysphagia and Trismus - Dramatically increased
with the use of ChemoRT

6. Radiation of Head and Neck Tumors
Impact of these changes
v Incidence of post treatment morbidity is rising
" Trismus – Dramatically increased with the use of ChemoRT
" Velopharyngeal insufficiency and velopharyngeal
incompetence - Dramatically increased with the use of
ChemoRT
" Osteoradionecrosis - Dramatically increased with the use of
ChemoRT when conventional radiation therapy is employed.
Incidence still unknown when ChemoRT is used with IMRT
v Current literature
" Is it particularly helpful given the changes? Not particularly.

7. Radiation of Head and Neck Tumors
We also need to be familiar with the methods of
radiation treatment used previously.
v Conventional radiation
v Hyperfractionation
v Accelerated fractionation
v Brachytherapy
Why? Because many postradiation patients present with dental issues and
the long term tissue effects are dependent on dose levels and the volume of
tissues exposed high doses.

8. Biologic Effects
v Nucleus 100 to 1000 times more
sensitive than the cytoplasm
v Most damage
" Mitotic apparatus
" DNA

9. High Dose Radiation
Immediate Cell Death Reproductive DNA Damage
(Interphase Death (Functional Cell)
Spontaneous Trauma
Necrosis
Induce Proliferation
(Reproductive Death)
Induced proliferation and cell
death after irradiation.

10. Induced proliferation and cell death
after irradiation.
XRT

11. Modalities
v External radiation therapy
v Radiation is delivered via an external source
v CRT - Conventional lateral facial fields that are
usually equally weighted
v IMRT
v Brachytherapy
v The modality of radiation therapy that utilizes
radioactive isotopes within capsules, needles, tubing
etc. inserted into body cavities (intracavitary) or into
tissues and organs (interstitial).

12. External Radiation Therapy
Photon beam therapy*
v Superficial (50 keV to 150 keV) - was used for
treatment of small superficial skin tumors
v Orthovoltage (150 keV to 300 keV) – was used to treat
superficial but thick tumors of the skin
v Megavoltage (1 MeV or greater, like cobalt and linear
accelerators) – used to treat deeply situated tumors
while sparing superficial normal tissues (“skin sparing”)
*Used for most oral and pharyngeal tumors

13. External Radiation Therapy
Particulate Radiations
v Electronbeam
v Neutron beam
v Proton beam
Electron beam is the most commonly employed. It allows
for delivery of high doses of radiation to tumors located
within 6 cm of the surface. The energy of the beam can
be adjusted to the depth of interest. Neutron beam and
Proton beam therapy are not widely available and are still
considered experimental.

14. Mixed Beam
v Combination of electron beam plus
photon beam
v Often used in the treatment of parotid
tumors or large skin tumors

15. Units of Dosage
v The unit of radiation dose is called the gray and is
defined as the energy absorption of 1 joule per
kilogram of tissue.
v This has replaced the rad, which corresponds to
to an energy absorption of 100 ergs/gm.
v Therefore, 1 rad equals 1 centigray (cGy).

16. Fractionation
Radiation is delivered in a series of treatments or
fractions. They average around 200 cGy per fraction
and are generally delivered over a 6-7 week period.
Total dose when conventional fractionation is used,
ranges from 6600-7200 cGy.

17. Fractionation -Scientific rationale:
v Allowsfor reoxygenation of hypoxic,
radioresistant tumor cells
v Cell cycle dynamics
v Redistribution of cells within the cell cycle tends to sensitize the
more rapidly dividing cells in the tumor
v Repopulation of cells between fractions
permitting regrowth of normal cells
v Normal cell recovery vs tumor cell recovery
v Normal cells have a greater capacity to repair sublethal damage
than tumor cells

18. Fractionation
Hyperfractionation
v Number of fractions per day increases as does total dose, and
the total number of fractions. Treatment time remains the same
and dose per fraction averages about 120 cGy per fraction as
opposed to 200 cGy used in conventional fractionated therapy.
Accelerated fractionation
v Slight decrease in the dose per fraction which ranges from 140
cGy to 160 cGy and is given twice or thrice daily. Overall dose is
the same or less and treatment time is reduced.

19. Fractionation Schedules
Dose Fractions Per Day Time
Conventional 7000 35 200 times 1 7 weeks
Hyperfractionation 8050 70 115 times 2 7 weeks
Accelerated 7200 45 160 times 3 3 weeks
Hyperfractionated/ 5400 36 150 times 3 12 days
Accelerated

20. Fractionation
Hyperfractionation
Acute side effects were more severe than conventional
fractionation protocols (Denham et al, 1999) but the late effects
appeared to be less although good clinical data is still not
available.
Hyperfractionation and accelerated fractionation were used
primarily in the treatment of large unresectable tumors,
such as this lesion, that ordinarily would be difficult to
control with conventional fractionation protocols.

21. Changing methods of radiation delivery
Conventional radiation therapy (CRT)
l 200 cGy per fraction
l Total doses
l 7000 cGy definitive dose
l 5000-6000 cGy post op Source: www.beaumonthospital.com
Intensity modulated radiation therapy (IMRT)
This technique uses multiple
radiation beams of non-uniform
intensities. The beams are
modulated to the required
intensity maps for delivering
highly conformal doses of
radiation to the treatment
targets, while limiting dose to
adjacent tissues.
Source: www.beaumonthospital.com

22. Dosimetry
The purpose of dosimetry is to evaluate
the amount of energy absorbed by the
tissues subjected to radiation
Isodose curves
v Graphic displays of dose patterns through
tissues
v These characteristics will vary with the type
and the energy of the radiation applied
and can vary significantly between
machines used to generate these beams

23. Isodose Curves
High energy photons are used primarily for deeply situated tumors whereas
particulate beam is used for more superficial tumors. Sometimes they are
used in combination.
Photon Beam Cobalt 60 Particulate Radiation - Electron Beam
Isodose of photon beam Isodose curves of electron beam. Note rapid
(Co60). Note progressive falloff of tissue dose.
falling off of tissue dose and
that maximum dosage level
(100%) is attained below skin High energy photons are skin sparing
surface

24. Isodose Curves
Multiple Beams
v Prior to IMRT multiple beams were used to treat deeply situated tumors in
order to deliver a dose to the tumor equal to or higher than the dose
delivered to adjacent normal tissues
v Concentration of dose was achieved by using two converging photon
beams and wedges (tumor of ethmoid and maxillary antrum).

25. Methods
v CRT
v Radiation is delivered via
bilateral opposed equally Source: www.beaumonthospital.com
weighted fields
v IMRT
v Radiation delivered
externally from multiple
angles
Source: www.beaumonthospital.com
v Brachytherapy
v Radioactive sources are
implanted locally within the
tissues encompassed by
the tumor

26. Conventional Radiation (CRT)
External Radiation - Fields
Size, extent and clinical ramifications
Simulation film Port film
Prior to the advent and widespread use of IMRT, most oral cavity tumors were
treated with bilateral opposed, equally weighted fields. This field was used to
treat a patient with a nasopharyngeal carcinoma.
Note how the field has been reshaped to avoid the mandibular molar area.

27. Conventional Radiation (CRT)
External Radiation - Fields
Size, extent and clinical ramifications
Simulation film Port film
The high posterior fields used for treatment of soft palate, tonsillar and
nasopharyngeal tumors include substantial portions of the parotid glands and
submaxillary glands. The resultant reduction in salivary flow predisposes to
radiation caries. The risk of osteoradionecrosis, however is low when this type
of field was used.

28. Conventional Radiation (CRT)
External Radiation - Fields
Size, extent, and clinical ramifications
Simulation film Port film
Opposed mandibular fields seen here were used to treat tumors arising
from the floor of the mouth and anterior two thirds of the tongue. They
expose most of the mandibular body to high doses of radiation and as a
result the risk of osteoradionecrosis is high. However, in these patients
much of the parotid glands are spared. Consequently, the risk of caries
is reduced.

29. Conventional Radiation (CRT)
External Radiation - Fields
Simulation Initial Radiation Off Cord Boost
Film Field Field Field
During treatment radiation fields were often reduced in size. For
example, the initial field is used to carry the dose to 5000 cGy. The
“off cord” field brings the tumor dose to 5500 - 6000 cGy. The boost
field encompasses only the primary lesion and brings the tumor dose
to approximately 7000cGy.

30. Intensity modulated radiation therapy
(IMRT)
Advantages: Reducing the dose local tissues
receive from high dose radiation such as salivary
glands and bone
Concerns: Underdosing the primary tumor and
nodal areas

31. IMRT
v IMRT dose distribution diagrams. Note that higher dose per
fractions are centered on clinical tumor volume. Note how
parotid tissues receive a lower dose.
v If parotid dose (pink) can be kept below 30 Gy postradiation
salivary flow will be close to normal.

32. IMRT
Source:www.Beaumont
hospitals.com

33. IMRT dosimetry diagrams
Note the hot spot on anterior mandible (oval)

34. Brachytherapy
Definition – The modality of radiation therapy
that utilizes radioactive isotopes within capsules,
needles, tubing etc. inserted into body cavities
(intracavitary) or into tissues and organs
(interstitial).

35. Brachytherapy
v Iridium 192 seeds are most commonly used today. They are used primarily
in T1 and T2 localized carcinomas of the oral tongue and floor of the mouth.
v Most patients receive 5000-5500 cGy of external beam to the tumor volume
and the nodal bed followed by a boost provided with brachytherapy.
Advantages:
v Dose to the buccal side of the mandible on the side of the tumor is
generally limited to the dose delivered by the external therapy. This level
(5000-5500cGy) of radiation is not sufficient to totally eliminate the fine
vasculature of these tissues.

36. Isodose Curves - Brachytherapy
Isodose curves of iridium implants positioned in the floor of
the mouth. Note rapid falloff of tissue dose as distance from
sources increase. As a result the tissue effects of the
radiation are localized. The oral mucositis is confined to the
tissues in and around the implant.

37. Brachytherapy – Clinical Significance
Prior to therapy teeth on the side opposite the implant can be treated
more conservatively than those adjacent to the implant. Teeth adjacent
to the implant should be considered for removal prior to therapy.

38. Chemoradiation
(CRT) (IMRT)
Source: www.beaumonthospital.com Source: www.beaumonthospital.com
v In combination with CRT or IMRT
v Full course of concomitant chemoradiation is theoretically
equivalent to an additional 700-1000 cGy (Kashibhatla, 2007,
Fowler, 2008).
Consequences (particlularly with CRT):
More short term and long term side effects (mucositis, trismus, dysphagia,
velopharyngeal function, osteoradionecrosis).

39. Indications and key facts
Most malignant neoplasms of the mucosa of the head and neck are
v
squamous carcinomas of various radio- sensitivities.
v Primary lymphomas and adenocarcinomas are relatively rare.
v Sarcomasand melanomas are also rare and are primarily surgical
diseases that require wide margins. These margins may not be possible in
the head and neck region without undue morbidity, so treatment often
combines surgery and postoperative radiotherapy.

40. Indications and key facts
v Chemoradiation is generally the treatment of choice for
carcinomas arising from the nasopharynx, base of tongue,
tonsil and soft palate because of surgical morbidity or
difficult access.
v Carcinomas of the alveolar ridge and salivary glands should
be treated surgically, due to the potential for bone I
infiltration (alveolar ridge), and then possibly followed by
radiation therapy.

41. Indications and key facts
v Early carcinomas of the tongue and floor of mouth are equally well
controlled with either surgery or radiation therapy.
v When conventional fractionation and external radiation is used
doses are in the order of 6600 to 7200 cGy in 6 to 7 weeks.
v Local tumor doses from interstitial therapy can be higher.

42. Indications and key facts
v Lymphnode metastases are fairly radiocurable when they are
less than 2 cm in diameter.
v Tumorsexhibiting deep invasion of soft tissue or extension
into bone or cartilage are less likely to be controlled with
radiation alone, and a planned combined approach with
surgery and/or chemotherapy may be considered.

43. Indications and key facts
Indications for postoperative radiotherapy
include:
v Positive and/or close surgical margins
v Residual gross disease
v Tumor spillage
v Perineural invasion
v Lymphovascular invasion
v Multiple positive nodes
v Extracapsular extension
v The known recurrence pattern

44. Immediate Tissue Changes
Seconds, minutes, hours after initial
exposure
v Free radical formation
v Disruption of molecular bonds
v Breaks in DNA strands

45. Initial Tissue Effects – Early Changes
v Swelling, degeneration and necrosis of the inner
endothelial lining of small arteries and arterioles.
v Loss of endothelial lining leads to formation of thrombi
which occlude the smaller vessels.
v These changes lead to increased permeability of vessel
walls which in turn leads to increased vascular
congestion.
v Increased amounts of perivascular fluid exerts pressure
on the walls of small vessels further impeding blood
flow.
Result: Metabolic support for surrounding tissues is
impaired leading to fibroblastic activity and fibrosis.

46. Long Term Tissue Changes
v Cardiovascular system – Blood vessels
v Musculoskeletal system
v Hematopoietic tissue
v Skin and mucosa

47. Long Term Tissue Changes
Blood Vessels*#
v Microcirculation
v Thrombosis
Results in net
v Telangiectasia
loss of vascular
networks
v Occlusion of vessel lumens
v Small and medium sized arteries
v Formation of intimal fibrotic plaques Results in
v Fibrosis of the muscular walls anoxia, cell
v Foam cell plaques in the intima death and
v Perivascular fibrosis
fibrosis
*These changes, are responsible for many of the injurious side
effects of radiation on a variety of cells and body tissues.
#The cells most responsible for the long term damage are
fibroblasts and the intimal cells of the blood vessels.

48. Late Effects – Telangiectasia
Telangiectasia
v Represents dilation and coalescence of capillaries and small
venules in the lamina propria (mini aneurysms). They have been
described as a contraction of 10-20 capillaries into one
microaneurysm. Telangiectasias significantly reduce blood flow to
the area.
v Indicates that the epithelium is 5-6 cell layers thick and is easily
perforated

49. Long Term Tissue Changes
Musculoskeletal system
v Bone
" Trabeculae loose their osteocytes
" Marrow becomes avascular, acellular
and fibrotic
" Continued osteoclastic activity
" Periosteum exhibits fibrosis with
atypical fibroblasts

50. Long Term Tissue Changes
Musculoskeletal system
Muscle
v Atrophy –
v Velopharyngeal incompetence
v Impaired tongue function
v Fibrosis and Muscle contracture
v Trismus
v Pain with motion

51. Long Term Tissue Changes
a b
Examples of muscle wasting and fibrosis of
heavily irradiated tissues.
a: Patient presented with velopharyngeal insufficiency with
hypernasal speech and nasal leakage during swallowing.
b: Patient presented with compromised speech articulation
secondary to reduced bulk and mobility of tongue.

52. Long Term Tissue Changes
Hematopoietic tissue
Very radiosensitive
v Fatty and fibrous degeneration
v Complete absence of hemopoietic activity
v Loss of stem cells
v Negative impact on osseointegration

53. Long Term Tissue Changes
Skin
v Atrophy
v Hyperpigmentation or
depigmentation
v Dryness
v Alopecia
v Chronic ulceration
v Scarring
v Telangiectasia

54. Long Term Tissue Changes
v Velopharyngeal insufficiency - Secondary to muscle
wasting and fibrosis
v Cranial neuropathies – Secondary to fibrosis of the
nerve trunk and loss of myelin sheaths
v Caries – Secondary to compromise of the quality and
quantity of saliva. Loss of salivary parenchyma is primarily
caused by fibrosis and loss of its vasculature.
v Trismus – Secondary to contracture of the muscles of
mastication secondary to fibrosis and atrophy associated
with the loss of vasculature.

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57. References
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