HYPERBARIC OXYGEN THERAPY IN THE TREATMENT OF
RADIO-INDUCED LESIONS IN NORMAL TISSUESCONSENSUS CONFERENCELong Version

Jointly held by:

EUROPEAN SOCIETY FOR THERAPEUTIC RADIOLOGY AND ONCOLOGYAND
EUROPEAN COMMITTEE FOR HYPERBARIC MEDICINE

October 19-20th, 2001
Lisbon – Portugal

1Introduction
Format of the Conference
Conference Report
Question 1:
What are the incidence and the cost of the radio-induced lesions in normal
tissues?
Question 2:
What tissue changes induced by radiotherapy lead to impaired healing inradio-injured normal tissues?
Question 3:
What is the rationale for Hyperbaric Oxygen Therapy in the treatment ofradio-induced lesions in normal tissues?
Question 4:
What are the locations of radio-induced lesions where hyperbaric oxygentherapy has shown efficacy?
Question 5:
May hyperbaric oxygen therapy play any role in the prevention of radioinduced tissue lesions?
Question 6:
Is hyperbaric oxygen therapy cost effective in these indications?
Future Research2Introduction
Surgery, radiation therapy and cytotoxic chemotherapy are the principal methods
employed in the treatment of cancer. Although all have achieved considerable
advances in the attainment of cure all are associated with a risk of morbidity andmortality. Radiation therapy differs from the other two modes of treatment in that its
most serious associated morbidity tends to occur months and commonly years after
treatment when management is often difficult and unsatisfactory.
It has been estimated that within the European Union there are five million people
alive at five years or more after having received radiation therapy as the principal oras an adjuvant method of treatment. Although the large majority are fit and well withlittle or nothing to relate to the treatment given, troublesome symptoms may bepresent in up to 5% due to late radiation changes. Perhaps as many as 1%, that is,
50,000 people, may have serious problems, which are resistant to simple methods oftreatment. Major surgery may be required as well as prolonged hospital care.
Personal and social problems may be very distressing and commonly those affected
are unable to pursue gainful employment.
Because a dominant feature of post-radiation change is the obliteration of small
blood vessels leading to hypoxia, hyperbaric oxygen has been employed in the careof these patients. In the past forty years there have been many publications reporting
benefit in studies, which have included some thousands of patients.
Because the literature is dominated by case series containing modest numbers andby case reports and because there have been few randomised trails, there isconsiderable uncertainty as to the place of hyperbaric oxygen in the management ofradiation morbidity. The importance of the problem led the European Society of
Therapeutic Radiology and Oncology and the European Committee for Hyperbaric
Medicine to jointly organise a Consensus Conference, so that the evidence could be
reviewed and guidance drawn up as to clinical practice.

3Format of the Conference
After listening to evidence, a jury drawn from authorities in the areas of medicine
concerned, were asked to answer six questions covering the field of concern.
The jury and those attending the conference were informed by two highly detailed
literature reviews:(i)Radio-Induced Lesions in Normal Tissues: Incidence, Risk Factor andConventional Treatment.
Dr David Pasquier, Centre Oscar Lambret, Lille, France(ii)

Hyperbaric Oxygen Therapy in Radionecrosis (A review of the literature).
Dr Jorg Schmutz, Hyperbaric Center, Basel, Switzerland

Nine experts prepared written reviews often with the assistance of colleagues andgave presentations which extended through the whole of the first day of theconference:
(iii)

(iv)

(v)

(vi)

(vii)

(viii)(ix)(x)

Professor Michael Baumann
Carl Gustav Carus, Dresden, Germany
Incidence, risk factors and cost of radio-induced lesions in normal tissues.
Written review by: Baumann, M. Holscher, T.
Professor Bernard Dubray
Centre Henri Becquerel, Rouen, France
Pathophysiological basis of radiation-induced lesions in normal tissues.
Written review by: Dubray, B. Lefaix, J-L. Martin, M. Delanian, S.
Professor Gosta Granstrom
Goteborg Universitat, Goteborg, Sweden
Pathophysiological basis for HBO in the treatment of healing disorders inradio-injured normal tissues.
Written review by: Granstrom, G.
Professor Johannes Van Merkesteyn
Leiden University Medical Center, The Netherlands
Hyperbaric oxygen therapy in the treatment of osteo-radionecrosis.
Written review by: Van Merkesteyn, J
Professor A J Van der Kleij
Academic Medical Center, Amsterdam, The Netherlands
Hyperbaric oxygen therapy in soft tissue radionecrosis. Radio-induced
cystitis.
Written review by: Van der Kleij, A J. De Rijke, T. Hulshof, M.
Dr F Roque
Hospital da Marinha, Lisboa, Portugal
Hyperbaric oxygen therapy for late radio-induced intestinal lesions.
Written review by: Roque, F. Saraiva, A. Simao, G. Sousa, A. Torres, P.
Sampaio, J.
Professor J Yarnold
Institute of Cancer Research, Sutton, Surrey, UK
Hyperbaric oxygen therapy in soft tissue radionecrosis: Radiation-induced
myelitis and plexopathy.
Written review by: Yarnold, JR. Gothard, L.
Professor John Feldmeier
Medical College of Ohio, USA
Hyperbaric oxygen: Does it have a cancer causing or growth enhancing
effect?

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(xi)Written review by: Feldmeier, J.
Dr A Marroni
Centro Iperbarico Ravenna, Italy
A cost-benefit evaluation of hyperbaric oxygen use in tissue radio-induced
lesions.
Written review by: Marroni, A. Longobardi, P. Cali Corleo, R.

After each presentation there was a vigorous discussion amongst the 150 attendees
who were physicians and surgeons with an interest in hyperbaric oxygen or radiation
oncologists.

On the second morning there was a three-hour session of the jury. The members
were:Stanley Dische, President
Professor in Oncology – Centre for Cancer Treatment – Mount Vernon
Hospital – UK
Dirk Bakker
Professor of Surgery – Academic Medical Center – Amsterdam – The Netherlands
Karl Hartmann
Department of Radiation Oncology – University of Dusseldorf – Germany
Ferran Guedea
Head of the department of Radiation Oncology – Institut Catala d’Oncologia –Barcelona – Spain
Joaquim Gouveia
Director Hospital Cuf-Descobertas/Former Director Instituto Portugues de Oncologia– Lisboa - Portugal
Eric Lartigau, ESTRO General Secretary
Professor in Radiation Oncology – Centre Oscar Lambret – Lille – France
Daniel Mathieu, ECHM General Secretary
Professor in Critical Care Medicine – Centre Hospitalier Universitaire – Lille – France
Advising the jury were –David Pasquier
Centre Oscar Lambert – Lille – France
Jorg Schmutz
Hyberbaric Center – Basel – Switzerland
After the meeting of the jury there was an immediate report to the conference by the
President of the Jury. A written report was drafted by the President and circulated to
all members of the jury for comment, addition and deletion before presentation for
publication.

5

Conference Report
The jury discussed all the evidence put before it and came to recommendations forclinical practice. In assessing the quality of the evidence, the scale: 1 (strong), 2(convincing evidence), 3 (existing but weak evidence) and 4 (anecdotal evidence)
was employed (Table 1).
The jury were grateful to the eleven reviewers who worked so hard to collect andanalyse the evidence, which they had considered. These valuable reviews, whichwere at a high standard of scholarship, will be published on the web of ESTRO(www.estro.be), so as to be generally available. In this report the reviews will bereferred to by the Roman numbers as noted above.
Question 1:
What are the incidence and the cost of the radio-induced lesions in normal tissues?
The jury was grateful to Professor Michael Baumann for his review of the subject. It
was the modification of the late effects by use of hyperbaric oxygen that was theconcern of the meeting and the incidence was much influenced by the definition andgrading of the late changes. There was unfortunately no internationally agreed
grading system but the greatest experience was with the RTOG/EORTC system
available for over thirty years and the LENT-SOMA, which was developed from it andpublished in 1995. Other systems such as the Franco Italian glossary and thedictionary approach had been proven of value in randomised clinical trials.
International agreement as to the definition of morbidity would advance knowledge inthe field. The Mitre Meeting held in Brussels in December 2000 effectively reviewed
systems, which might be employed in routine practice. There was to be a meeting in
Florida in April 2002 to try to make further advance in this field. The Conference
gave its encouragement towards the pursuit of agreement in this area.
The hardest evidence as to the incidence of morbidity is contained in reports ofrandomised controlled clinical trials but some can be gained from reports ofconsecutive series. These have been reviewed by Dr Pasquier [i] and the incidence
figures varied very widely according to definition and site. Even with one site acommon range was from less than 1% to over 30%. There was no doubt that theincidence of late damage using the older techniques of radiotherapy, particularly theuse of ortho-voltage apparatus, was considerable and has reduced with theemployment of high energy equipment, with improvements in patient immobilisation,
the introduction of precise planning using simulators and with greater precision indose definition and delivery. Further improvements, such as advanced planning sothat treatment is "conformal" to the tumour target volume and the use of intensity
modulated radiotherapy, should spare normal tissue damage.
There were, on the other hand, developments in oncology, which might reverse thistrend. "Conformal" radiotherapy has encouraged the attainment of higher tumour
doses and inevitably some normal tissues will be included. The concomitantadministration of cytotoxics where an adjuvant effect is likely to increase theincidence of late damage and the quantitative importance of these drug radiationinteractions are difficult to predict. An increasing use of major surgery for restorationof function or for salvage of advanced recurrent disease is also associated with ahigh risk of morbidity when a heavily irradiated area is operated upon.
The maximum tolerable radiation dose is often set as that which produces anincidence of 5% of moderate or severe late damage. The number of patients withsevere damage that is resistant to simple measures is likely in actual fact to be much6

smaller. However, a prevalence of 1% does represent a very large number ofpatients in need of care.
The risk factors are similar over all sites and include the total radiation dose, theoverall time, the biological effective dose which takes into account fraction size andthe overall time, the volume irradiated, the use of a combination of external beamwith an implantation or intracavity procedure, a high dose rate with brachytherapy,
tumours adjacent to or involving bone, the presence of infection, the use of surgery
and the occurrence of trauma.
Although we need better data concerning the incidence of late damage due toradiotherapy in routine practice the level of evidence to support the observations
about incidence which we have made is extensive and certainly can be regarded as
being at level 1/2.
Professor Baumann could find very little useful evidence to answer the question
concerning the cost of morbidity. Dr Marroni, in his contribution [xi] concerned withcost effectiveness, has reviewed two papers from the United States concerned withmandibular radionecrosis where the average yearly costs of care reached $140,000
Much of the cost was due to hospitalisation and drugs and these figures did notinclude costs due to loss of work and care at home. Dr Marroni presented data from
Italian hospitals suggesting that over 3000 patients in the year 2000 were discharged
with a diagnosis of “radio-lesions of the mandible and soft tissues» and these didseem to represent a high cost to the Italian Health Service. Dr Marroni also gavesome evidence suggesting that hyperbaric oxygen treatment would considerably
reduce the cost. The jury had some uncertainty about the reliability of this data but it
did give some support to the view that the costs of care for radionecrosis were
extremely high and that these might be reduced with the use of hyperbaric oxygen.
Overall the current evidence was regarded to be at level 3, that is, weak.

Question 2:
What tissue changes induced by radiotherapy lead to impaired healing in radioinjured normal tissues?
When heavily irradiated tissues are examined at an interval of months or years after
treatment the characteristic findings are a cellular depletion, fibrosis and a reduction
in vascular density with marked narrowing of the small blood vessels. There is
therefore hypoxia due to the vascular changes. . Professor Granstrom [v] described
the changes, which may be observed in irradiated tissue.
Professor Bernard Dubray reviewed the subject and stressed the inter-relationshipbetween these three types of change. The exact mechanism of production of thesechanges is undoubtedly complex and incompletely understood. Molecular biology
has shown that hypoxia could trigger altered gene expression leading to a whole
range of effects. Use of hyperbaric oxygen in these circumstances may also lead tocomplex changes, which may not all be favourable.
There is laboratory and clinical evidence that interstitial fibrosis and necrosis can, atleast in part, be reversed by drugs such as exogenous SOD or a combination ofPentoxifylline and vitamin E. The mechanism whereby the benefit is gained remains
obscure and Professor Dubray expressed the need for better knowledge of radiationinduced late damage in normal tissues
The jury felt that there was some level 4 and considerable level 3 evidence to support
the views expressed.

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Question 3:
What is the rationale for Hyperbaric Oxygen Therapy in the treatment of radioinduced lesions in normal tissues?
This subject was fully reviewed by Professor Granstrom (v). He considered papers,
which gave evidence that there could be an increase in vascular density in irradiatedskin and soft tissues after treatment with hyperbaric oxygen. There was further
evidence using bone densitometry that new bone formation capacity could be
increased. In a controlled study in rabbits where implants had been performed there
was evidence of a significant increase in the force necessary to unscrew implants. In
another animal study hyperbaric oxygen increased the capacity for osseo-integration.
Further it has been found that hyperbaric oxygen could stimulate bone maturation.
Experimental studies of animals with myocutaneous flaps showed significantly
increased vascularity with hyperbaric oxygen. It was found that steep oxygen
gradients stimulated macrophage angiogenesis factor and macrophage derived
growth factor. Bone healing in mice was enhanced.
There was evidence at a similar level which suggested that in patients, hypoxia wasa major component of delayed wound healing because a reduced fibroblast activity
and less efficient production of collagen. Hyperbaric oxygen inducing a temporary
increase in the oxygen supply stimulated angiogenesis and modified fibrosis.
The jury considered there was a real rationale for hyperbaric oxygen to be used inradiation-induced morbidity as gained from these studies. The evidence was at level
1 and level 2.

Question 4:
What are the locations of radio-induced lesions where hyperbaric oxygen therapy has
shown efficacy?
Mandibular osteo-radionecrosis:
Here there was a large body of evidence [i,ii & vi].
The conservative management combines the use of antiseptic solutions, analgesics,
oral hygiene, systemic antibiotics and simple sequestrectomy. Lesions less than
1cm in maximum diameter commonly heal but larger lesions tend to be refractory,
however very varied healing rates are reported in the literature [I].
When conservative measures fail then surgery, often mandibulectomy with complex
reconstructive work becomes indicated. These procedures tend to be followed bypost-operative complications, which tend to be great when a large area of heavily
irradiated bone must be incised.
Hyperbaric oxygen has been used in the management of osteo-radionecrosis forforty years and it has often been employed with radical surgery, benefit rates of 30100% have been reported but the situation is complex because surgery is also
employed in a number of the published series.
There is no randomised controlled trial of the use of hyperbaric oxygen in this area.
However, impressive margins healing have been reported when comparison has
been made with previously treated cases. There were seven studies recorded since
1993 with improvements noted in 70-92% of the cases included in each series (ii).

8In this situation where conservative treatment for gross mandibular radionecrosis canachieve at best a minimal healing and where commonly there may be progression of
the process the results achieved in the management of consecutive cases can begiven considerable importance. The proportion of cases showing improvement inmany of the series was impressive. The jury felt that there was a considerable bodyof evidence to support a view that hyperbaric oxygen was effective in improving
osteo-radionecrosis of the mandible and that it should be considered as part ofmanagement when conservative measures fail to allow healing to take place (level 2
evidence).
There was a wide variety of clinical presentation of osteo-radionecrosis of themandible and the use of hyperbaric oxygen alone or in combination with surgery
would need to be decided according to the features of a particular case.
Osteo-radionecrosis at other sites:
There was a body of literature concerned with the treatment of bone necrosis at othersites and these included the maxilla, spine and pelvic bones. Many of thecontributions to the literature were anecdotal and the tendency for publication to be of
positive results and lack of interest in publishing negative results must lead to somereservation. However, with the evidence for benefit in osteo-radionecrosis of themandible, hyperbaric oxygen therapy could be considered as a possible method to
employ in refractory cases of osteo-radionecrosis at other sites than the mandible3).
Radionecrosis of the larynx:
Here there was some evidence of benefit. Five papers reporting a total of 45 caseswith publication dates between 1976 and 2000 were available (ii). In general the
majority of the patients appeared to benefit, however, the evidence must be regarded
as weak and at level 4. Hyperbaric oxygen could be employed in this situation.
Radiation cystitis:
Here there was a considerable literature and fifteen papers reporting a total of 256
cases have been published since 1989 (ii). Haematuria was a dominant symptom,
one which was relieved in many cases. Frequency and incontinence was also
reported as improved in some cases. Professor Van der Kleij gave us a full review ofthe subject. Radiation cystitis occurred after radiotherapy for pelvic tumours, withincidence figures varying from less than 1 to over 30%. However, much depended
on the radiotherapy given and the criteria for reporting the complications.
Conservative treatment included antibiotic therapy, corticosteroids, blood transfusion,
bladder irrigation and Tocopherol.
Intervention included irrigation of the bladder with alum and installation of formalinsolution. These measures can be effective but the use of formalin may be
associated with major complications.
Limited cysto-diathermy and laser
photocoagulation may also be employed in the management of small areas of
bladder where the sites of bleeding can be demonstrated.
Surgery in the form of a urinary diversion, an ileo-cystoplasty or a cystectomy withdiversion may be employed. Operations performed in the heavily irradiated pelvis
are associated with a high risk of further morbidities.
A recent literature review from Oxford identified 309 references where many different
forms of treatment were employed. They concluded in the absence of randomised
studies that it is impossible to set definite rules for treatment.

9

The jury were however impressed that in patients resistant to conservative treatment
and where the only measure to be considered was cystectomy, there was a high rateof response to hyperbaric oxygen; while recurrence of bleeding did occur in some,there were a considerable number where the improvement was maintained longterm. The jury therefore considered that there was convincing evidence (level 2) thatin this situation hyperbaric oxygen should be employed in management.
There was possibly a place for hyperbaric oxygen at an earlier stage when thesimplest methods of treatment had failed to gain a response. Further this was a
logical development but its adoption must depend upon the result of a randomised
controlled clinical trial.
Radiation-induced proctitis and enteritis:
Here there was a considerable literature which had been gathered [I, ii & vi] for review
by the conference and the jury. Fifteen papers reporting 256 cases treated withhyperbaric oxygen were found and there were 10 papers reporting 116 cases from1993 to 2000 (i,ii). The majority of the cases were reported as either cured or
improved with regard to the symptoms and/or clinical findings. In their review Dr
Roque and his colleagues found 13 papers reporting 107 cases between 1990 and
2000, and gained an even greater impression of improvement (viii). The symptoms
and findings in these cases were obviously complex, making assessment difficult.
The jury concluded that hyperbaric oxygen could be employed in the management ofradiation proctitis and enteritis, however the evidence must be regarded as at level
three (weak).
Radiation plexopathy:
The review by Dr Yarnold assisted by Mrs Gothard reviewed radiation induced
myelitis and plexopathy. A randomised controlled trial involving 31 patients withbrachial plexopathy performed by Dr Yarnold and his colleagues had yielded noevidence for benefit but the study, though performed with great care, wasconsiderably underpowered. There were, in addition, a number of anecdotal reports
concerning the use of hyperbaric oxygen for brain necrosis and radiation myelitis,
however the evidence was unconvincing. There was therefore considerable
uncertainty as to the place of hyperbaric oxygen in the treatment of radio necrosis incentral nervous system and we could therefore come to no recommendation as
regards its place in management.
Other sites
Evidence was presented concerning the use of hyperbaric oxygen at other sites,
which included skin, the subcutaneous tissues, the eye and breast. The largest bodyof evidence was with regard to the breast where there may be a place for hyperbaric
oxygen however the evidence must be regarded as weak (level three)

Question 5:
May hyperbaric oxygen therapy play any role in the prevention of radio-induced
tissue lesions?
a) Tooth extraction in irradiated tissues
Here there was considerable evidence gathered by our reviewers [eye,ii,v & vi].
Included was a randomised controlled trial performed by Marks [v, p.87] and theresult was supported by other studies reporting consecutive cases where acomparison was made with cases managed without hyperbaric oxygen. The jury
felt that there was convincing evidence (levels 1 and 2) that in a situation where
teeth extraction was planned in an area of mandible or maxilla which had

10received high dose radiotherapy, hyperbaric oxygen importantly reduced the riskof osteo-radionecrosis. However some evidence was presented that the risk of
tooth extraction in irradiated tissue was normally so low that hyperbaric oxygen
was unnecessary as a preventative measure. It was however felt by the jury thatin this report case selection may have played a role in that the radiation doses
may have been moderate and so the risk may have been so low as to makehyperbaric oxygen unnecessary. This was obviously an area where radiation
oncologist and surgeon must collaborate together to assess the site, volume andradiation dose so as to determine the indication. It was also obviously an area forfurther randomised studies.
b) Surgery in irradiated tissue
Considerable evidence was brought before the jury that post operativecomplications could be reduced by the use of hyperbaric oxygen when major
surgery was planned in previously irradiated patients. Wound infections anddehiscence were significantly reduced as well as delayed wound healing reported
as serious. No randomised controlled study has however taken place. The jury
felt it was an area where hyperbaric oxygen may well have a place but theevidence remained weak in the absence of a randomised controlled trial
published in peer-reviewed journals, which is always necessary when a measurefor prevention is being assessed.

c)Implants in irradiated tissues
There is an increasing use of implantation of metal prostheses into heavily
irradiated tissue as restorative surgery is increasingly used in patients who haveextensive resections and radiotherapy for advanced tumours. There wasevidence suggesting that hyperbaric oxygen could have a role but it must be
regarded as weak and again a need for a randomised controlled clinical trial was
clear.

Question 6
Is hyperbaric oxygen therapy cost effective in these indications?
An important consideration in a patient with malignant disease was the possibility that
there could be a harmful effect of hyperbaric treatment. Professor Feldmeier gave usa most interesting review of this subject. The question first arose over forty years
ago when patients were being treated by radiotherapy in hyperbaric oxygen
chambers. Dr Feldmeier effectively reviewed the subject and showed that theevidence that hyperbaric oxygen disseminated tumour and led clinically to a higher
incidence of distant metastasis was extremely weak and the jury were convinced that
this was not a problem. In patients who suffered post-radiation phenomenon thelarge majority were, of course, free of tumour so this was not a problem to evenconsider.
The evidence produced in reviews (iii) and (xi) has already been considered. The
jury felt that there was so little hard evidence in this field that it was not possible toreach a conclusion. Costs of hyperbaric therapy could be measured but even here it
was necessary to consider the personal and social costs as well as that of the actual
treatment. The cost of radiation morbidity itself is obviously high but until real data
was available it was not possible to determine whether hyperbaric oxygen would truly
have a cost-saving effect. Their impression was that this would be the case but
presently this could not be substantiated by hard evidence.

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Future Research
The Consensus Conference did reveal many areas where research was required inorder to advance knowledge and to lead to evidence-based decisions as to the placeof hyperbaric oxygen in the management of late radiation morbidity.
The jury felt that data should be gathered concerning:
1.

The incidence of post-radiation morbidity in routine practice. An internationallyagreed simple system for recording such morbidity would be an essential
prerequisite
2. Cost of radiation morbidity.
The jury felt that randomised controlled clinical trials were indicated in the clinicalsituations:
1. Where tooth extraction is planned in areas, which have received radiotherapy, butwhere the post-radiation change is not gross so as not to be included in the groupwhere the jury felt that hyperbaric oxygen was already indicated.
2. In patients who are planned for extensive restorative surgery and/or prosthetic
implantation after large volume radiotherapy to tumourcidal dosage.
3. Patients with irradiation cystitis after simple methods of management had failed
but before the stage at which cystectomy/urinary diversion had become indicated.
The jury felt that these were all areas where, on a European basis, in a close
collaboration between physicians and surgeons concerned with hyperbaric oxygen
and radiation oncologists, together with surgeons called on to operate in postradiation situations, trials could be established, performed at a high standard andrecruit sufficient numbers of patients.

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Table I : Scale used to assess the evidence presented.

Level

Grade

Definition

Level 1

Strong evidence of beneficial At least 2 concordant, large,
action.
double-blind,
controlled
randomised studies with no or
only weak methodological bias.

Level 2

Convincing
evidence
beneficial action.

Level 3Evidence of beneficial action but Only
uncontrolled
studies :weakly supported.
historic control group, cohort
study, …

Level 4

Anecdotal evidence of beneficial Case
reportonlyoractionmethodological or interpretation
bias preclude any conclusion.

of Existenceofdouble-blind
controlled, randomised studies
but with methodological bias, orconcerning only small sample, oronly a single double-blinded,
controlled, randomised study.

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Table II : Indications of HBO in the treatment of radio-induced
lesions in normal tissues

Recommendation grade
Level 2 – convincing evidence

Indication
Radionecrosis of the mandible
Radiation Cystitis of the bladder resistant
to conservative measures
Tooth extraction in irradiated tissues(preventive action)

Level 3 - Evidence of beneficial action but Radionecrosis of other bones
weakly supported.
Radiation-induced proctitis and enteritis
Radiation-induced lesions of soft tissues
Surgery and implants in heavily irradiatedtissues (preventive action)

Level 4 – anecdoctal evidence

Radiation-induced lesions of the larynx
Radiation-induced lesions of the central
nervous system.

No evidence to support

Radiation-induced plexopathy

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