9.(new)osteoradionecrosis

Osteoradionecrosis
John Beumer III, DDS, MS,
Eric Sung, DDS
Division of Advanced Prosthodontics
UCLA School of Dentistry

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Osteoradionecrosis
Definition – Exposure of bone within the radiation
treatment volume of 2-6 months duration or longer

Pathogenesis – 3 Hypotheses
Meyer (1970)
v Irradiated bone subjected to a traumatic event could lead to a
superimposed infection similar to osteomyelitis

Marx (1983)
v 3H theory of ORN. Following radiation, formulation of hypoxic-
hypocellular-hypovascular tissue (3H) then tissue breakdown, and finally
a nonhealing wound as ORN

Delanian and Lefaix (2004)
v ORN is due to the activation and dysregulation of fibroblastic activity. A
cascade of cytokines and free radicals leads to the destruction of
endothelial cells and vascular thrombosis, which leads to necrosis of
micro-vessels, local ischemia and tissue loss. The combination of death
of osteoblasts, failure of osteoblasts to repopulate, continued
osteoclastic activity and excessive proliferation of myofibroblasts, results
in bone matrix being replaced by fibrous tissues.

Staging System
Schwartz and Kagan (2002)
v Stage I – Superficial
involvement of the mandible
with minimal soft tissue
ulceration: only the exposed
cortical bone is necrotic

v Stage II – Both the exposed
cortical bone and the underlying
medullary bone are necrotic

v Stage III – Full diffuse
involvement of the mandible,
including a full thickness
segment of bone.

Osteoradionecrosis - Sequellae
Why is this such an important sequellae
of radiation therapy?

Because advanced cases may lead to fistula
formation as is seen in this patient . . . .

prolonged exposures of bone intra-orally,

pathologic fractures of the mandible and . . .


. . . mandibular discontinuity defects with
accompanying mandibular deviation,
disruption of speech, mastication and
saliva control, and facial deformity.

Osteoradionecrosis – Key Facts
Principle cause – Loss of vasculature
v Severe narrowing of the lumens of the facial and inferior alveolar
arteries
v Loss of the fine vasculature of the bone marrow and the Haversian
systems of lamellar bone
v Bone matrix replaced by fibrous tissues.

Affects the mandible to a much greater degree
than the maxilla
v More than 90% of all osteoradionecrosis arise in the mandible
v Most osteoradionecrosis (ORN) arising from the maxilla heals with
conservative treatment and does not require hyperbaric oxygen.
Exceptions – ORN’s secondary to chemoRT or Neutron beam therapy.

Osteoradionecrosis - Key Facts
The incidence varies depending on total dosage, clinical tumor
volume, fractionation, modality and dental disease factor

v As low as 3% (Beumer et al, 1972) and as high as 37% (Grant and Fletcher,
1966) when high energy photons are used

v Higher when brachytherapy is used

v Extremely high when neutron radiation therapy is used (NRT) (Marunick
2000)

v Fewer than 5% of all osteoradionecrosis occurs in edentulous patients
(Beumer et al, 1984).

v Increased risk associated with concomitant chemotherapy (Kuhnt et al,
2006; Hehr et al, 2006)

Osteoradionecrosis - Contributing Factors
High Energy Photons

v CRT and Radiation fields – If external beam is used
alone, the more the body of the mandible in the field
the greater the risk of osteoradionecrosis (ORN).

v IMRT may decrease the risk

v Dose to Bone – Below 6500 cGy or equivalent the risk
is very low and almost all that develop in this dosage
range heal with conservative measures and do not
require hyperbaric oxygen therapy.

v ChemoRT - Increases the risk of ORN and treatment
is less predictable.

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

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
structures adjacent

High Energy Photons
IMRT - Volume of the mandible receiving doses in excess of
6500 cGy is reduced

Osteoradionecrosis - Contributing
Factors
High Energy Photons with CRT

Dose to bone
v 6500-7000 cGy – rate of bone necrosis is
5-15%
v 7000-7500 cGy – rate of bone necrosis is
15-50%
v 7500 and above - rate of bone necrosis is >
50%

Will these numbers hold with IMRT?

Osteoradionecrosis - Contributing

Chemotherapy increases the risk!!!
vA full course of concomitant
chemotherapy increases the Biologic
equivalent dose (BED) by 700-1000 cGy

*If the patient received concomitant chemotherapy,
a serious bone necrosis leading to resection of the
mandible can occur at doses as low as 5000 cGy.

Modality – Brachytherapy
External beam vs combined external beam and
brachytherapy. When the dose is boosted
locally with brachytherapy with multiple sources
positioned close to or on the mandible, the dose
to bone locally can be quite high and the patient
is at great risk of developing an ORN.

*When the dose to the local bone exceeds 7500
cGy, the risk of osteoradionecrosis is 50% or more.

Incidence of Osteoradionecrosis
According to Radiation Dose to Bone
Incidence of bone necrosis
Dose to bone (cGy) Dentulous Pts Edentulous
<6500 0/36 (0%) 0/3 (0%)
6500-7500 8/29 (28%) 1/15 (7%)
7500 11/13 (85%) 2/4 (50%)
Total 19/78 (24%) 3/22 (14%)

Source: Morrish et al, Cancer 47, l980

Osteoradionecrosis
Predisposing and precipitating factors
1960’s - 2000
1. Postradiation extraction of teeth within the
radiation field
* 2. Spontaneous associated with dental infection
3. Preradiation extractions
4. Spontaneous: Dose delivered beyond tolerance
of normal tissues
5. Denture irritation
6. Placement of osseointegrated implants into
irradiated bone

*Most common factors until chemoRT

Osteoradionecrosis
Predisposing and precipitating factors since 2000

1. Spontaneous associated with dental infection
* 2. Spontaneous: Dose delivered beyond tolerance of
normal tissues
3. Preradiation extractions
4. Postradiation extraction of teeth within the radiation
field
5. Denture irritation
6. Placement of osseointegrated implants into
irradiated bone

*Most common factors since chemoRT

Osteoradionecrosis – predisposing factors (cont’d)
Postradiation extraction of teeth within the
radiation treatment volume-Maxilla

In most patients, maxillary teeth in the radiation field
can be extracted post radiation, with little risk of
osteoradionecrosis. Even if an ORN develops as
shown here, the nonvital areas of bone sequestrate
naturally, leaving only small local bony deformities.


Both these osteos developed following extraction of teeth after
radiation therapy. Both patients received in excess of 6600 cGy
to the extraction sites. Conservative treatment was employed
(local irrigation, removal of loose sequestra of bone etc.) and
both healed several months after onset.


Exceptions:
v Patients treated with concomitant chemotherapy
v Patients treated with neutron radiation therapy (NRT)

ORN’s associated with these treatment modalities
are frequently intractable and do not respond to
any form of treatment including HBO.

Osteoradionecrosis-predisposing factors
radiation treatment volume-Mandible

Post radiation extraction of
mandibular teeth in the field of
radiation when the patient receives
in excess of 6500 cGy is risky and
often leads to osteoradionecrosis.

Osteoradionecrosis-predisposing factors
radiation treatment volume-Mandible

All four of these patients presented with squamous
carcinomas of either the oral tongue or floor of the
mouth and were treated with external beam photons
and opposed mandibular fields. All received in excess
of 6600 cGy and developed ORN after postradiation
extractions.

All patients developed ORN before the introduction of hyperbaric oxygen and
all eventually had major portions of their mandibles resected resulting in
discontinuity defects in order to control the infection.

Postradiation extractions*
Ill advised in the mandible if the dose to bone is
above 5500 cGy unless accompanied by HBO
or the pentoxyfilline-tocopherol protocol
Incidence of osteoradionecrosis secondary to postradiation extractions
Patients Osteos

Grant and Fletcher, 1966 16 7 44%
Beumer et al, 1984 40 11 28%
Morrish et al, 1980 18 11 61%
Marx, et al, 1984 37 11 30%

Totals 111 40 36%

*In these clinical reports the dose to bone was in excess of
6500 cGy and the patients did not receive HBO.

Osteoradionecrosis – Predisposing factors
Preradiation extraction of teeth within the
radiation treatment volume
A In contrast, most
ORN secondary to
preradiation
extraction, such as
these, heal with
conservative
B measures.

Most are confined within the attached gingiva
(Stage I) and the gingival fibers help maintain the
attachment of the periosteum to underlying bone,
providing blood supply to the underlying bone and
preventing expansion of the bone exposure.

Osteoradionecrosis – Predisposing factors
Preradiation extraction of teeth within the
radiation treatment volume
Both patients shown
A developed ORN at
preradiation extraction
sites. Both had been
treated with external beam
photons and the extraction
sites had received in
excess of 7100 cGy.
B
B

Most ORN that develops at preradiation
extraction sites stays localized within
the zone of attached tissue and can be
treated successfully with conservative
measures (patient B). Resolution of this ORN
took 8 months.

Preradiation extractions

Number of patients 120
Osteoradionecrosis directly associated with
extraction sites 12

Only one of the 12 patients developing ORN associated
with preradiation extractions required mandibular
resection and developed a discontinuity defect of the
mandible.

From Beumer et al, 1984

Osteoradionecrosis – predisposing factors
Spontaneous associated with acute
periodontal infections

All five of these patients presented with
similar histories- bone exposure sites
treated in excess of 6600 cGy, previous
history of pain and swelling, followed by a foul smelling
discharge, with eventual pain relief accompanied by
exposure of bone.

Spontaneous associated with acute
periodontal infections
v Osteoradionecrosis of the mandible that develops as a
result of periodontal infections after radiation therapy is most
serious (particularly if the Radiotherapy was delivered with
external beam) because many result in discontinuity defects.
v Upon initial presentation most ORN developing in this way
extends deep within the body of the mandible (Stage II or III),
and often the lingual or buccal periosteum is dissected away
as the bone exposure enlarges.

The periosteum is the prime source of blood supply and its loss
results in divitalization of the underlying bone, leading in most
patients, to surgical resection of a portion of the mandibular body.

Secondary to denture irritation

A B

Most ORN secondary to denture irritation is
not serious as long as it is confined to the
residual attached gingiva (Stage I)(A), and
heal with conservative measures.

Secondary to denture irritation

A

B

Both these ORN’s developed in association with denture wear.
In patient “A” the bone exposure developed 7 months after
insertion at the site of a preradiation dental extraction and was
probably caused by a particle of food becoming lodged beneath
the denture. In patient “B” the probable cause was an
overextended denture flange. Both patients received over 6900
cGy via external beam but both healed with conservative
measures and did not require hyperbaric oxygen.

Spontaneous – Dose delivered beyond
normal tissue tolerance

Both these patients were treated with a combination of
external beam photons and brachytherapy and developed
ORN adjacent to the sites of placement of iridium implants.
Both received over 8500 cGy to the lingual surface of the
mandible.


Both these patients were treated with concomitant
chemoradiation and the BED (biologic equivalent dose) to the
posterior body of the mandible approached 8000 cGy


This patient was treated with concomitant chemoradiation and
the BED (biologic equivalent dose) to the maxilla approached
8000 cGy. Eventually the entire maxilla was lost.

Osseointegrated implants

Only a limited number of anectodal case reports
are available for review. The inicidence will
probably be similar to that seen in patients
undergoing post radiation extraction.

Osseointegrated implants

v This patient received 6600 cGy via opposed mandibular fields for
a squamous carcinoma of the oral tongue. Implants were
placed 6 years after completion of therapy.

v Three years after placement the patient developed an infection on the
lingual side of the left posterior implant (arrow). Eventually an oral
cutaneous fistula developed followed by a pathologic fracture of
the mandible.

The mandible was resected and reconstructed with a fibula free flap.

Osteoradionecrosis
Goal of treatment – Resolution with
maintenance of mandibular continuity

Osteoradionecrosis –Treatment Options
v Conservative – Local irrigation, regular followup, removal of
loose sequestra and debridement as appropriate
v Hyperbaric oxygen protocol - HBO combined with surgical
debridement or resection
v Pentoxifylline – tocopherol protocol

Stage I
If the ORN is confined within the
zone of attached gingiva and not
directly associated with the
dentition, conservative measures
are recommended.

v Hyperbaric oxygen (HBO) combined with surgical debridement,
resection and closure
v Pentoxyfilline – tocopherol protocol

Stage II and III
Does the exposure extend
beyond the mucogingival
junction? Is there evidence of
bone resorption along the inferior
border of the mandible? If so,
either the HBO protocol or
pentoxifylline tocophoral protocol
should be considered .


What has been its clinical course? Is the exposure getting worse?
If so, either the HBO protocol or the pentoxifylline tocophoral
protocol should be considered .

Initial presentation 3 moths later


What was the mode of therapy? If the dose
to the primary was boosted with
brachytherapy, what was the dosimetry of
the implant.

vIf unfavorable, either the HBO protocol or
pentoxifylline protocol should be considered.

vIf favorable and the external beam dose was
below 5500 cGy, conservative therapy can be used.


vRadical neck on the side of the ORN, continued alcohol and
tobacco abuse etc? These factors would encourage the use of
the HBO protocol or the pentoxifylline-tocopherol protocol.

vIf adjunctive or concomitant chemotherapy is used in
combination with radiation, the HBO protocol or the
pentoxifylline-tocopherol protocol should be considered.

Osteoradionecrosis
Predictors of treatment outcomes
v Initial presentation
v Stage I - Does the ORN extend beyond or is it within
the zone of keratinized attached mucosa?
v This is an important prognostic factor because, in
general, ORN that extends beyond this zone has a
poor treatment outcome.

Osteoradionecrosis
v Initial
Presentation and precipitating factors-
Osteoradionecrosis that is precipitated by:
v Postradiation extractions – Generally extend beyond the
zone of attached keratinized mucosa and extend into the
underlying medulary bone. These by definition would be
Stage II
v Periodontal infections – Generally extend beyond this
zone. Most would be Stage II

These initiating factors generally imply a poor outcome

Osteoradionecrosis
vInitial Presentation and precipitating factors-
Osteoradionecrosis that is precipitated by:
vPreradiation extractions – Generally stay within this
zone. Most are Stage I
vDenture irritation – Generally stay within this zone.
Most are Stage I.

These initiating factors generally imply a good outcome

Osteoradionecrosis
vMode of radiation treatment
vCombined external beam and brachytherapy:
Generally such ORN is locally confined and heals with
conservative therapy if the dosimetry of brachytherapy
is favorable.
v External beam alone: If the ORN occurs in the
mandible in a high dose area the outcomes are less
favorable.
vConcomitant chemoRT: ORN’s in these patients
generally do not respond to conservative measures,
HBO or the pentoxyfilline – tocopherol protocols and
require resection and reconstruction with a free flap

Osteoradionecrosis
Goal of treatment – Resolution with
maintenance of mandibular continuity
Predictors of treatment
outcomes
vDose and Treatment Volume
vThe higher the dose and the larger the treatment
volume the less predictable the outcome.

Osteoradionecrosis-Treatment
ORN extending beyond the mucogingival junction
as is seen in these two patients
• When it does so, and the radiation is delivered via
external beam, HBO should be considered.

vIs there evidence of
bone resorption
associated with
trabecular bone or the
inferior border of the
mandible as seen
here?
vIf so, HBO should be
considered.

Osteoradionecrosis-Treatment
ORN extending beyond the mucogingival junction
as is seen in these two patients
• When it does so, and the radiation is delivered via
external beam, HBO should be considered.

Osteoradionecrosis-Treatment Decisions
and Clinical Examples
Is there evidence of bone resorption associated
with trabecular bone or the inferior border of the
mandible as seen here?
If so, HBO should be considered.

Eventually patient suffered a pathologic fracture of the mandible.

Clinical course - Has the bone exposure
enlarged to extend beyond the mucogingival
junction?
• If so, HBO should be considered.

Initial presentation 3 months later

Brachytherapy, tumor dose and the dose to the
local bone - What was the dosimetry of the
implant?

If the dosimetry associated with
the implant is favorable, i.e., the
total dose to the inferior border
and the buccal plate is below
5500 cGy, conservative
measures are recommended
even if the ORN extends
beyond the mucogingival
junction.

Post-radiation dental disease
Post radiation
extractions
and HBO
l Dose to Mandible is
greater than 5500
cGy
l Expensive and
time-consuming

Treatment of Osteoradionecrosis - Summary
Role of Conservative Therapy
v ORN confined within the zone of attached
keratinized mucosa that is stable or improving.
v ORN in patients treated with brachytherapy with
favorable dose distribution.
v Initial treatment for an ORN when the dose to
bone is below 6500 cGy and delivered with
external beam and conventional fractionation.

Treatment of Osteoradionecrosis - Summary
Role of Hyperbaric oxygen
v ORN that extends beyond the mucogingival junction in
patients treated solely with external beam therapy where
the dose to bone is in excess of 6500 cGy using
conventional fractionation.
v ORN precipitated by periodontal or periapical infections
when the patient has been treated with high dose external
beam therapy.
v ORN associated with brachytherapy that extends beyond
the mucogingival junction that does not respond to
conservative therapy and where the dosimetry associated
with the implant is unfavorable.
v ORN resulting in significant resorption of bone extending
to the inferior border of the mandible.


Other factors to consider*
v Radical neck dissection on the side of
the ORN. The facial artery, which
supplies feeding vessels to the lingual
periosteum, is removed during this
procedure.
v Continued alcohol and tobacco abuse
v Poor oral compliance

*Thesefactors would favor the use of the
HBO or pentoxyfilline-tocopherol protocols.

Osteoradionecrosis
Role of surgical debridement
v Incombination with HBO or the pentoxifylline
- tocopherol protocol
Role of surgical resection and
reconstruction
v When conservative therapies have failed
v When patient presents with history of high
dose radiation in combination with
concomitant chemotherapy

Osteoradionecrosis – Role of Conservative Therapy
Clinical Examples
This patient was S/P 5500 cGy delivered with
external beam plus 2500-3500 cGy via an
iridium implant for a squamous carcinoma of
the right lateral tongue and floor of the mouth.
Two years later he developed an ORN on the
lingual surface of the mandible.
Evaluation of the dosimetry of the implant
revealed most of the treatment volume
confined to the lingual surface of the mandible

Exam revealed the ORN to be
undermined by the oral epithelium and
loose. Removal was accomplished
with cotton pliers revealing normal
epithelium beneath. Eventually all the
teeth exfoliated and the remaining
bone exposures sequestrated
spontaneously.

Osteoradionecrosis-Role of Conservative Therapy
Clinical Examples
This patient received 5500 cGy with external beam with the
linear accelerator plus 2500-3500 cGy via an iridium implant.
Two years later he developed an ORN on the left lingual surface
of the mandible.
Nonvital bone was removed with a
high speed air rotor with copius
irrigation. After several episodes
mucosal coverage was attained.

Close examination
reveals that the
bone exposure was
being undermined
by oral epithelium.

Exception
High Dose Rate Implants
l Technique sensitive
l It is very easy to deliver excessive doses
when using this technique

Osteoradionecrosis-Role of Conservative Therapy
Clinical Examples
• This patient is S/P 7100 cGy with external beam photons for
treatment of a squamous carcinoma of the soft palate.
Opposed lateral facial fields were employed.
• Six months after therapy he developed an ORN at the site of
a preradiation extraction.
• The ORN was confined to the attached gingiva.
After 8 months of
conservative
therapy the ORN
had resolved.

Osteoradionecrosis – Treatment with HBO
Clinical Examples
• ORN associated with external beam
• If the ORN extends beyond the mucogingival
junction and the dose to bone is above 6500cGy
(with conventional fractionation) or its biological
equivalent, hyperbaric oxygen combined with
surgical sequestrectomy is recommended.

Clinical Examples
This patient presented S/P 7100 cGy delivered with external
beam for a squamous carcinoma,with an ORN of the right lingual
surface of the mandible. Note that the exposure extends beyond
the mucogingival junction.
Following a course of hyperbaric oxygen
(30 treatments), surgical excision of the
nonvital bone and extraction of teeth in
the local area was accomplished.

Another ten HBO treatments were administered. The wound
re-epithelialized and mandibular continuity was maintained.

Osteoradionecrosis-Treatment with HBO
Clinical Examples
l This patient presented with a bone exposure after
therapy at a preradiation extraction site. He had
received over 9500 cGy to the right body of the
mandible. He continued to smoke and drink
heavily.
The necrosis continued to
The exposure began to enlarge and eventually the
enlarge and so the patient entire body of the mandible
was referred for a course of was resected and later
HBO. reconstructed.

HBO is effective when the tissues are still viable but delay in
the face of high dosage may compromise the chance of
success and result in greater bone loss.

Clinical Examples
This patient presented with a small ORN on
the lingual of #29 and #30 secondary to a
periodontal abscess. Four years earlier she
had received 5500 cGy with external beam
plus another 4500 cGy via an iridium implant.
Note the bone loss associated
with these teeth

Hygiene was excellent and
the patient had ceased
using tobacco or alcohol.
Note that the labial gingiva
appears quite healthy.

Clinical Examples
Conservative
therapy was
initiated but the
ORN increased in
size.

•HBO combined with surgical debridement was recommended
but the patient refused. The exposure progressed until the
lingual plate from molar to molar was exposed and the patient
developed an orocutaneous fistula.

•The patient finally accepted HBO and a series of
treatments were initiated combined with biweekly irrigations
and debridement.

Eventually a large segment of nonvital
bone was undermined by oral epithelium,
became loose and was removed with
cotton pliers. The oral cutaneous fistula
closed.
Appearing beneath, was a bed
of granulation tissue and oral
mucous membrane. However,
small localized areas of exposed
bone still remained.

Osteoradionecrosis - Treatment with HBO
l One month later most of the
granulation tissue had been
covered with oral epithelium

During the next 18 months
the small residual areas of
exposed bone became
undermined by oral
epithelium and sequestrated
sometimes helped along with
a high speed air rotor.

Three years later most of the teeth had exfoliated and the
patient was fitted with a removable partial denture.

Eventually all the mandibular teeth exfoliated. Note the
telangiectasia associated with oral mucosa and the atrophy of
the tongue. A complete denture was fabricated for the
purposes of lip support and esthetics and well tolerated by the
patient.

Why was the outcome successful?
•The dosimetry of the implant was favorable.
Although the implant delivered a high dose to a
large volume of tissue, the dose to the inferior
border and buccal cortical bone of the mandible
was low (only slightly above 5500 cGy)
•The external beam dose was low – 5500 cGy. At this level the
periosteum and marrow retain significant vascular elements.

•The patient was compliant. The patient
stopped smoking and her oral hygiene was
superb. She never missed an irrigation
appointment.
Hyperbaric oxygen. These
treatments revascularized the
marginally necrotic tissues and
facilitated the patient’s response to
the local infections.

Osteoradionecrosis –Treatment with Surgical
This patient developed an ORN following
postradiation extractions. He had
received 6600 cGy for a squamous
carcinoma of the right lateral tongue.
However, a localtreatment was initiatated
Conservative surgical sequestrectomy
was attempted which resulted in the stable
and the bone exposure remained
exposure extending beyond the zone of
and began to improve.
attached gingiva. The exposure rapidly
expanded, eventually extending lingually to
the inferior border of the mandible.

Pathologic fracture and an
orocutaneous fistula soon
followed and the mandibular
body was eventually resected in
Clinical Examples order to resolve the infections.

Why was the outcome so unsuccessful?
• The patient continued to smoke and use alcohol.
• All the radiation was delivered with external beam
photons. The tumor dose was 6600 cGy and the
dose was distributed homogenously from the
buccal side to the lingual side of the mandibular
body.
• At these dosage levels the vascularity and
cellularity of the periosteum was severely
compromised and no longer provided sufficient
vascular support to the underlying bone.
However, as long as the periosteum remained
attached to underlying bone, the bone remained
viable.
• When the mucoperiosteum was dissected away

Why was the outcome so unsuccessful?
• As long as the exposure was confined within the
attached mucosa, it did not spread because the
gingival fibers helped to maintain contact
between the periosteum and cortical bone.

• Once the exposure had spread beyond the
attached mucosa, the attachment of periosteum
to the underlying bone became very tenuous.
The slightest infectious insult will dissect the
atrophied periosteum from the underlying bone.
When dissection occurs, the bone looses its
primary remaining blood supply and becomes
essentially nonvital. HBO will not salvage such a
mandible and its resection is inevitable.

Osteoradionecrosis – Case report
l This patient presented with an ORN 18 months post radiation.
It is not painful, there are no draining fistulas and a panorex
reveals little change in the density of the trabecular bone or
the cortex of the inferior border of the mandible. The exposure
has been present for about 3 months and extends beyond the
mucogingival junction lingually. What radiation data do you
need to acquire before developing a plan of treatment?

Mode of therapy
Dose to bone
Dosimetry

What patient data do you need to obtain?

Oral Compliance
Smoking habits
Medical history

Osteoradionecrosis – Case report
l The patient received 5000 cGy to the tumor volume and the
neck with external beam high energy photons. The dose to
the primary was boosted with an iridium implant with an
additional 2500-3500 cGy. The CT generated dosimetry is
shown here. What treatment do you recommend?
Conservative therapy was employed. Bone
undermined by oral mucosa, was periodically
removed with a high speed air rotor. Within 9
months the nonvital bone had been removed and
mucosal integrity was restored.

Osteoradionecrosis - Case report
l This patient was treated with external beam high energy
photons and brachytherapy for a squamous carcinoma of the
right lateral tongue. Two years after completion she
developed an acute periodontal infection which eventually led
to dehiscence of the lingual gingiva and an
osteoradionecrosis. What information do you need to
develop a plan of treatment for this patient?
Radiation data
• Fields of external beam
• Dosimetry of the implant
• Dose to bone of the buccal
half of the mandible

Other data
Oral compliance
Smoking habits
Updated MH

Osteoradionecrosis – Case Report
• Dosimetry was very favorable. Since the implants had
been placed into the lateral border of the tongue, the
dose delivered to the middle of the mandibular body
by the implant was minimal.
• The dosage delivered to lingual plate was about 2000 cGy.
• Oral hygiene was poor, however, and the patient
continued to use tobacco.

What treatment would you recommend for this patient?

Osteoradionecrosis-Case Report
Conservative therapy was adopted because the
external beam dose to the mandible was low
and the dosimetry of the implant was favorable.

The premolar and the cuspid exfoliated and the
nonvital bone sequestrated within 9 months.
Eventually all of the remaining teeth exfoliated.

Osteoradionecrosis – Surgical Management
Free vascularized flaps and myocutaneous
flaps can be used to cover exposed areas of
bone following surgical sequestrectomy.

The nonvital bone is removed surgically and a flap
is used to cover the remaining bone. In this patient
a pectoralis myocutaneous flap was used.

Osteoradionecrosis – Surgical Management
Reconstruction with fibula free flaps

Potential problems with free flap reconstruction
vSemi-occluded vessels in the neck with fibrotic and
fragile walls.
vComplication rate -50%
Suh et al, 2010
vRelapse rate about 25 %

Osteoradionecrosis:
Treatment Philosophies
Marx
• Dr. Marx and his colleagues believe
almost all osteoradionecrosis of the
mandible would benefit from hyperbaric
oxygen treatment.

• What follows is the protocol developed
by Dr. Marx used to treat patients with
osteoradionecrosis.

Hyperbaric Oxygen (per Marx)
• Stage I – These patients present with ORN
but without pathologic fracture of the
mandible, orocutaneous fistula or
radiographic evidence of bone resorption of
the inferior border of the mandible.
• Thirty HBO treatments (2.4 atmospheres, 100% oxygen
for 90 minutes)
• At the end of 30 treatments, if improvement is noted,
another 10 treatments are administered.

If no improvement is noted, the patient is considered
a nonresponder and is advanced to Stage II.

• Stage II
• Nonresponders are taken to surgery and
surgical debridement of the local area is
performed. Nonvital bone is removed via a
transalveolar sequestrectomy and the labial
and lingual mucoperiosteal flaps are closed in
three layers over a base of bleeding
bone.
• An additional 10 HBO treatments are added.

If the wound dehisces, the patient is considered
a nonresponder and advanced to Stage III.

• Stage III
• Nonresponders from Stage II therapy, and patients
presenting with orocutaneous fistula, pathologic fracture of
the mandible or bone resorption of the inferior border of
the mandible, are considered Stage III patients.

• Following the initial 30 treatments, bony segments of the
nonvital mandibular bone are resected. Soft tissue deficits
if present are restored with local or distant flaps and
orocutaneous fistulas are closed

• Another 10 HBO treatments are administered and the
patient is advanced to Stage IIIR


• Stage IIIR
• Ten weeks after resection the
mandible is reconstructed with a
free bone graft, using a
transcutaneous exposure.

• Mandibular fixation is achieved and
the patient given another 10 HBO
treatments.

Hyperbaric Oxygen

l Permanence
l Patients restudied 4
years after HBO
demonstrated the same
angiogenesis as those
studied immediately
after completion.
l New hyperbaric induced
vessels do not appear to
involute after cessation
of HBO faster than the
normal rate of aging.

Osteoradionecrosis:
Reconstruction after Resection
v Free grafts vs free
vascularized grafts
Both methods achieve successful results in the hands of
experienced surgeons although the success rates associated with
the use of free grafts is enhanced by the use of hyperbaric
oxygen.

Potential problems with free flaps:
v Semi-occluded vessels in the neck with fibrotic and
fragile walls.
vRelapse

Osteoradionecrosis:
Patient is S/P resection of the mandible for an ORN. He had
received in excess of 6800 cGy to the body of the mandible with
external beam.
The defect was restored with a
block bone graft from the iliac
crest

Hyperbaric
oxygen was
unsuccessful in
saving the
continuity of the
mandible. One year S/P bone graft

Osteoradionecrosis:
Patient is S/P resection of the mandible for an osteoradionecrosis.
He had received in excess of 6800 cGy to the body of the
mandible.
The defect was restored with a
block bone graft from the iliac
crest

Six months later
osseointegrated
implants were
successfully
placed into the
grafted bone. One year S/P bone graft

Osteoradionecrosis – Prevention
Since Osteoradionecrosis (ORN) is a process that
primarily affects the mandible . . . . . and
since mandibular teeth are the prime precipitators
of ORN we recommend the following strategies.
Prevention strategies
Remove mandibular teeth with significant periodontal or
advanced caries in the field prior to therapy in high
dose areas.
Remove mandibular teeth adjacent to a prospective
iridium implant.

Osteoradionecrosis – Prevention
Since Osteoradionecrosis (ORN) is a process that
primarily affects the mandible and . . . . .
since mandibular teeth are the prime precipitators
of ORN we recommend the following strategies.

Prevention strategies
Remove all teeth within the gross tumor volume and the
patient is potentially noncompliant particularly in
patients who receive concomitant chemotherapy.

Soft Tissue Necrosis
Definition – A non-neoplastic mucosal ulceration
occurring in the postradiation field and which does not
expose bone
Most occur within a year of therapy and develop at the site of
radioactive implants or peroral cone application sites.

The key issue is to determine whether these ulcerations
represent recurrent tumor. Clinical symptoms useful in making
the diagnosis are:
a) Soft tissue necroses lack an inflammatory halo
b) Soft tissue necrosis is much more painful than tumor recurrence
c) Soft tissue necroses are not indurated, tumor recurrences are
indurated

Treatment
• Establish the diagnosis
• Local excision and primary closure
• Local supportive measures and
followup
• Hyperbaric oxygen

Patient received 5500 cGy via external beam and another
2500-3000 cGy with a radium needle implant for a squamous
cell carcinoma of the lateral border of the tongue.

v Nine months after therapy he developed this ulceration at the
site of the tumor.
v Cytology and biopsy were negative and a diagnosis of radiation
soft tissue necrosis was assumed.
v The lesion epithelialized 4 months later

Soft tissue necrosis secondary to chemoradiation

The remaining soft palate musculature was scarred and
atrophic and elevated poorly. There was little lateral wall
movement. The defect at the junction of the hard and soft
palate was easily obturated, but not the posterior
velopharyngeal defect

Chemoradiation
v Late effects of radiation are more
profound, i.e. risk of osteoradionecrosis is
higher at the lower doses.
v Treatment outcomes are less predictable
v The usual methods of treatment
recommended in this program of instruction
based on dosage and initial clinical
presentation may not apply and may not be as
effective when chemoradiation has been used.
v High relapse rate when using free flaps for
reconstruction

Neutron Radiation Therapy
(NRT)
Treatment outcomes are less predictable and
the incidence of ORN is higher
• The usual methods of treatment recommended in this
program of instruction may not apply and may not be as
effective.

Neutron Radiation Therapy (NRT)
• Treatment outcomes are less
predictable and the incidence of
ORN is higher
• In a report by Marunick et al (2000), 4 of 9 patients
treated for malignant salivary gland tumors arising in
the maxilla or the paranasal sinuses, developed
osteoradionecrosis.
• None responded to the methods of treatment
described in this program and eventually lead to
loss of the entire palate in most of the patients.

Osteoradionecrosis Secondary to
Chemoradiation
vSpontaneous – in most instances no known
causative factors
vNot responsive to HBO

ORN secondary to ChemoRT

l Dramatically higher rates in the maxilla
with poorer outcomes.

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9.(new)osteoradionecrosis

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