Controlled
Multy/monoplace
HBO
Professor Gösta Granström
Department of Otolaryngology,
Head and Neck Surgery
University of Gothenburg, Sweden
Address:
Sahlgrenska University Hospital
S-413 45 Gothenburg, Sweden
Tel: +46-31-3421276
Fax: +46-31-416734
E-mail: gosta.granstrom@orlss.gu.se
This protocol has been
adopted by the Working Group Oncology of COST action B14.
“This protocol
has been considered in detail, and accepted by COSTB14. This is a
multi-national group of experts in the field of Hyperbaric Medicine, appointed
nationally in each individual case, and organised and supported by the European
Commission. Thus, the work described has been subjected to extensive peer
review and amendment, and may be regarded as consistent with best practice in
the field of Hyperbaric Medicine”
COST B14 Working
Group Oncology:
DENMARK JANSEN
Erik C
POLAND SICKO
Zdzislaw
PORTUGAL SIMAO
Antonio
SWEDEN GRANSTRÖM
Gösta
SWITZERLAND SCHMUTZ Jorg
SMINIA Peter
UNITED KINGDOM HAMILTON-FARRELL
Martin H
Since
1965, an increasing number of patients have osseointegrated implants installed
in various parts of the skeleton. These implants were originally developed to
anchor dental bridges in edentulous patients. Since 1977, the concept has
spread outside the oral cavity, to be used among patients who have
malformations of the face, and tissue defects after cancer surgery or trauma.
Furthermore, patients who need amplification from a hearing aid due to a
conductive type of hearing loss can have a bone-anchored hearing aid attached
to an osseointegrated implant. There are also orthopaedic applications in that
amputees might have prostheses fastened on implants anchored in the extremities
or joint replacements based on the same concept. It is estimated that more than
3 million patients have had more than 10 million implants installed worldwide
since 1965, most of these for dental reasons.
Implant
survival depends on the region in which the implant is installed. The longest
follow-up reports exist for implants in the oral cavity. It is expected that
implants in the mandible may survive to more than 90% after 20 years. The
corresponding figure for the maxilla is 80%. Temporal bone implants remain in
place to 90% after 20 years, whereas implants in other parts of the
craniofacial skeleton are lost to a higher proportion.
It
is well known that compromised tissues have a reduced capacity to integrate and
maintain osseointegrated implants. Compromised tissues could appear after
surgery, burns, pharmacological treatment as chronic steroid treatment,
chemotherapy or after radiotherapy. The most common reason for a compromised
tissue among patients needing osseointegrated implants has been after
irradiation of malignant tumours (1).
From
experimental studies it is known that irradiated bone partly loses it’s
capacity to repair and new synthesise bone and mineralise the newly formed bone
(2). It thus would have a reduced capacity to accept osseointegrated implants.
HBO has in other experimental studies been shown to stimulate bone formation,
increase the bone turnover and especially bone maturation (3). It has also been
shown to improve osseointegration by increasing the bone-metal contact area,
the amount of bone inside the treads and to increase the removal torque
necessary to unscrew the implants (4).
In
clinical longitudinal studies implant failures have repeatedly been reported to
be higher if the patient has been irradiated prior to implant installation (5).
Several studies have also shown that adjunctive HBO might improve
osseointegration and thus reduce implant failures (6,7).
In
a recent debate in the U.S.A. these two statements have been questioned (8,9).
It has thus been stated that there is not a higher implant failure rate among
patients that have been irradiated to oral cancers and who have had
osseointegrated implants installed in the mandible. As a consequence there
would thus be no need for preventive measures using HBO.
If
such an attitude is spreading among clinicians, we would have to expect a
number of drawbacks from implant surgery in irradiated tissues as denuded bone,
dehiscence, infections, fistulation and ultimately osteoradionecrosis. In order
to get a better basis for judgement, a multicenter study designed to answer
these questions would be advocated.
To establish if osseointegrated implant failures are higher in previously irradiated tissues. To establish if HBO can be used to reduce implant failures in irradiated tissues.
Main
endpoint:
-
Survival of osseointegrated implants.
Secondary
endpoints:
-
Implant failure in relation to irradiation dose,
irradiation quality, time from irradiation to implant surgery
-
Implant failure in relation to anatomical region
-
Implant failure in relation to implant material
and design used.
Based
on data from reference (7) the expected difference between the study group and
control group after three year to be 80% (p<0.05); 48 participants (24 of
each group) would be needed. (Addendum 1).
Inclusion
criteria:
-
Patient needing osseointegrated implants in the
head and neck region that has been previously irradiated.
-
Patient treated at osseointegration clinic with
good relation to local HBO-centre and willing to report continuously data to
study centre.
-
Physical and psyhological fitness for HBO therapy.
-
Provision of written informed consent and
availability for follow-up.
Exclusion
criteria:
-
Patients with active cancer needing removal of
implants or other types of reconstruction, postoperative chemotherapy or
radiotherapy.
-
Previous HBO-therapy after cancer diagnosis.
-
Other contraindications according to HBO standards
Haemoglobin
Age
and gender
Implant surgery will be performed by the used standardised technique.
Type
of implant, length of fixture recorded
Abutment
type and length to be recorded
Region
of implant installation
Prosthetic
device recorded including anchorage to abutments.
Implant
survival at clinical follow-up recordings. These would be performed at three
months intervals during the first year, at six months intervals during the
following two years and thereafter at yearly follow-ups.
After
informed consent, patients will be randomised by study centre (Gothenburg) to HBO or not HBO.
According to randomisation, patients will receive an
oxygen treatment following one of two modalities:
-
HBO group:
20 HBO preoperatively (1 treatment per day, 5-7 days per
week) and 10 HBO postoperatively (with start no later than 3 days after
surgery), one treatment per day, 2.5 ATA, 100% O2, during 90
minutes. Accepted ranges will be 2.4 – 2.6 ATA, up to 10 min airbrakes will be
allowed every 30 minutes.
Treatments will be given in a multiplace hyperbaric
chamber, using a demand-system face mask or in a monoplace chamber.
-
non-HBO group:
No adjunctive treatment.
The
scientist making the statistical analysis will be unaware of the type of
treatment given to the patients.
Evaluation
of the patients will be performed on coded evaluation records, devoid of any
possible identification of the patient. All evaluation sets will be sent to a
central data gathering and analysis office.
Data
gathered will include
Clinical
stability of implants.
X-ray
recordings.
Mucosa
or skin adverse reactions.
Appropriate statistical analysis using Mantel's test (9) and Fisher's test for
paired comparisons (10).
1. Granström G, Tjellström A, Brånemark P-I,
Fornander J. Bone-anchored reconstruction of the irradiated head and neck
cancer patient. Otolaryngol Head Neck Surg 1993;108:334-343.
2. Jacobsson M, Nannmark U, Sennerby L. Acute
microvascular reactions to ionizing irradation in bone-anchored titanium
implants: a vital microscopic study. Int J Oral Maxillofac Impl 1987;2:193-196.
3. Johnsson K, Hansson Å, Granström G, Jacobsson M, Turesson I. The effect of HBO on bone-titanium implant interface strength with and without preceding irradiation. Int J Oral Maxillofac Impl. 1993;8:415-419.
4. Johnsson ÅA, Sawaii T, Jacobsson M,
Granström G. Turesson I. A histomorphometric study of bone reactions to
titanium implants in irradiated bone and the effect of hyperbaric oxygen
treatment. Int J Oral Maxillofac Impl 1999;14:699-706.
5. Granström G, Bergström K, Tjellström A,
Brånemark PI. A detailed study of titanium fixture implants lost in
irradiated tissues. Int J Oral Maxillofac Impl 1994:9:653-662.
6.
Granström G, Jacobsson M, Tjellström A. Titanium implants in the irradiated
tissue. Benefits from hyperbaric oxygen. Int. J. Oral Maxillofac. Impl.
1992;7;15-25.
7. Granström G, Tjellström A, Brånemark, P-I. Osseointegrated
implants in irradiated bone. A case-controlled study using adjunctive
hyperbaric oxygen therapy. J Oral Maxillofac Surg 1999;57:493-499.
8.
Larsen PE: Placement of Dental Implants in the irradiated mandible: A protocol
involving adjunctive hyperbaric oxygen. J Oral Maxillofac Surg 1997;55:967-971.
9. Keller EE: Placement of dental implants in the irradiated
mandible: A protocol without adjunctive hyperbaric oxygen. J Oral Maxillofac Surg
1997;55:972-980.
10. Mantel N: Ranking procedures for arbitrarely restricted observations. Biometrics 1967;23:65.
11.
Bradley JW: Distribution-free statistical tests. London, Prentics-Hall, 1968,
p68.
The
study is pending on approval from the local ethics committee.
Patient entry protocol 1 (this space for study centre only)
Centre code Patient code Date
Sex M F Age_____
Patient entry is reported
from
Doctor (name)
___________________________________________________________________
Clinic___________________________________________________________________________
Address
_________________________________________________________________________
Telephone _____________________________Fax_______________________________________
E-mail___________________________________________
Which is: tick
corresponding below
Surgical clinic: qOral surgery qMaxillofacial surgery qENT surgery qOther (specify)
Prosthetic
clinic: qProsthodontic qAnaplastology qOther (specify)
HBO-clinic: qMultiplace facilityqMonoplace facility qOther
Patient name only for your own records, not for study center
Family name____________________________First name_______________________________
Social
security number or corresponding____________________________________________
Patient entry protocol 2 (this space for study centre only)
Centre code Patient code Date
Patient
history of relevance
_______________________________________________________________________________
Cancer
treatment
Type
of cancer_________________Site____________________Differentiation______________
Date
of diagnosis qqqqqq (yymmdd)
Surgery,
What type_______________________________________________________________
Date
of surgery qqqqqq (yymmdd)
Radiotherapy, Type___________________________Fractionation________________________
Dose________________________________________Region__________________________
Start
of rt qqqqqq (yymmdd) End of rt qqqqqq (yymmdd)
Chemotherapy, qYes qNo
Type_______________Dose___________________Interval___________________________
Type_______________Dose___________________Interval___________________________
Type_______________Dose___________________Interval__________________________
Type_______________Dose___________________Interval___________________________
Is the patient clinically tumour free? qYes qNo
If no, excluded from further participation___________________________________________
This note only for your own records, not for study center: