ARTICLE
Auteur(s) : TH Clayton1, J
Tait1, C Whitehurst2, VM
Yates1
1Department of Dermatology, Lancaster Royal
Infirmary, UK
2PhotoTherapeutics Ltd, Altrincham, UK
accepté le 6 Septembre 2005
Photodynamic therapy (PDT) is an effective treatment modality for
non-melanoma skin cancers [1]. For dermatological indications, PDT
can be achieved by the convenient topical application of
5-aminolaevulinic acid (5-ALA) which, when activated by a specific
wavelength of tissue penetrating light (633 nm), causes an
irreversible oxygen dependent reaction that destroys target tissue.
Tissue healing is then via regeneration. PDT has been shown to be
as effective as cryotherapy or 5-flurouracil, but with fewer
adverse events [2]. There have been a number of clinical trials
reporting the benefits of PDT in treating Bowen’s disease and BCCs
[3, 4]. Several studies have reported complete response rates of
80-95% and an excellent cosmetic outcome [5]. Morton et al.
reported 100% clearance rates obtained in 20 lesions treated with
PDT [6].The British Association of Dermatologists (BAD) guidelines
advise that PDT is as effective as the other treatment modalities
for treating Bowen’s disease- excision, curettage and cautery,
cryotherpy, laser ablation and topical 5-fluorouracil [7]. The
treatment protocol for efficient PDT involves the application of
topical 5-ALA 4 to 6 hours prior to irradiation. PDT is therefore a
time consuming procedure that inevitably results in a degree of
inconvenience for the patient being treated. PDT is usually
performed in a hospital setting.Morecambe bay NHS Trust has a total
catchment population of 350,000, and within this large geographical
area there is only one centre that uses PDT, Lancaster Royal
Infirmary. Bowen’s disease and basal cell carcinomas (BCCs)
characteristically affect older patients who may also have
associated difficulties with mobility. Many of these patients
currently have to travel the long distances (up to 100 miles
return) to the hospital for treatment. Using a portable PDT light
source we were able to deliver PDT in a primary care/community
setting with the aim of providing a more convenient service for
patients. We performed this study to identify if community
delivered PDT was a viable treatment alternative for superficial
BCCs and Bowen’s disease.
Primary objectives
1. To identify if PDT could be carried out in successfully in a
community setting.
2. Using standardised questionnaires to compare the quality of
care and convenience to the patient of two treatment strategies:
5-ALA PDT performed in a community setting and 5-ALA PDT
administered in a hospital setting.
Secondary objectives
1. Comparison of the cost effectiveness of both treatment
strategies.
2. Tolerability and side effects of the treatment.
Materials and methods
Patients were included if they were in general good health with a
diagnosis of either Bowen’s disease or superficial BCC. The
diagnosis was confirmed via skin biopsy. Patients were excluded if
they were systemically unwell or had recurrent lesions.
A total of 50 patients were randomly allocated to receive PDT in
either a hospital or community setting. Verbal and written consent
was obtained prior to treatment. The local ethics committee
approved the study.
Protocol
Patients with lesions clinically suggestive of either superficial
BCCs or Bowen’s disease, underwent skin biopsies to confirm the
diagnosis. Those with biopsy proven superficial BCCs or Bowen’s
disease were enrolled into the study. Suitable patients received
comprehensive information regarding the nature of the study and
written, informed consent was obtained. Patients were randomised
into one of the two treatment groups. This was achieved by
recruiting the first 25 consecutive patients seen in the
dermatology clinic with biopsy proven Bowen’s or superficial BBCs
into the secondary care group, and the next 25 patients being
placed into the primary care group, thus reducing any selection
bias.
Topical 5-ALA in an oil-in-water emulsion 20% (w/w) supplied as
5-ALA in Unguentum Merck (Crawford Pharmaceuticals, Milton Keynes,
U.K.) was applied to the entire lesion with an areola of 2 ±
5 mm of disease free skin under occlusion using an adhesive
dressing (Tegaderm; 3M, London, Ontario, Canada). The area was
covered by light-proof non-adhesive dressings to prevent exposure
to ambient light.
The occlusive dressing and excess photosensitiser was then
removed and the lesion irradiated with the light source for between
20 and 80 minutes depending upon the size of the lesion. In cases
where multiple lesions were present, a maximum of 5 lesions was
treated. The light source used was a portable Xenon arc lamp (λ
630 nm ± 15 nm emission).
Irradiation was delivered by trained PDT nurses, either at the
department of dermatology at Lancaster Royal Infirmary, or in a
local general practice clinic room. Patients treated in the
community had the 5-ALA applied in their own home by a dermatology
specialist nurse, and were thus able to remain at home during the
5-ALA absorption phase. Subsequent irradiation of the required
lesions was then carried out at the patient’s local health centre.
Following the initial treatment all patients were asked to complete
a questionnaire that was designed to ascertain the distance each
patient travelled to the treatment centre, the mode and cost of
transport, and patient satisfaction with the treatment. All
patients were then reviewed at 8 weeks and 6 months by a consultant
dermatologist.
Results
The average age of patients who were treated with PDT was 71 years.
All 25 patients who had received treatment at their local health
centres were able to remain at home during the 5-ALA absorption
phase, thus enabling a shorter treatment time at the centre. Of
these, 100% were treated within 1-2 hours at the local centre and
88% received their treatment within 1 hour. The 25 patients treated
at the hospital were required to attend for application of the
photosensitiser and therefore the total treatment time at the
hospital was substantially longer, 8% of these patients spent over
6 hours at the hospital undergoing treatment. The majority of the
patients, 64%, who received PDT at the hospital had treatment times
of between 3-6 hours, only 28% had treatment times under 3 hours.
As expected there was no statistical difference between the
outcomes of the two groups at 6 months follow-up (figures 1 and 2).
Questionnaire analysis (table 1)
( Table 1 )24 out of 25 (96%) patients
treated in the community reported that they would have preferred
their treatment to be undertaken locally in a primary care setting.
Of those that were treated in the hospital 13 out of 25 (52%)
reported that they would have preferred to receive the treatment in
the community.
Table 1
|
Treatment centre
|
Total distance travelled to treatment centre/miles
|
Average distance travelled to treatment centre/miles
|
Travel time to treatment centre Number of patients < 30 min.
30 – 60 min. > 60 min.
|
Preference for community or hospital treatment Number of
patients
|
|
Hosp
|
Comm
|
|
Community
|
|
|
|
|
|
|
N = 25
|
55.55
|
2.22
|
25
|
1
|
24
|
|
Hospital
|
|
|
|
|
|
|
N = 25
|
491
|
19.64
|
12 10 3
|
9
|
13
|
Costing
The cost of a single treatment with PDT can be broken down to:
1. Xenon short-arc lamp leased and using smartcard, £80 per
lesion.
2. Photosensitiser: £24 (£70 for 4.5 g Porphyrin cream,
three lesions per tube if possible)
3. Nursing: £10/hr
4. Consumables: £5 (dressings, local anaesthesia, etc).
This does not include initial review and follow-up by a
dermatologist. The costing of PDT has been previously calculated in
a cost minimisation study evaluating all potential treatments for
Bowen’s disease, where a figure of £119 per PDT treatment was
reported [8]. The overall costs were lower in the group treated in
primary care. In most cases this reflected the increased transport
costs attending the hospital. A total of 10 patients who were
treated in the hospital stated that they would require an ambulance
to travel to the hospital. The average ambulance transport cost was
£75 per trip. As a result of the large distances involved the
ambulance service cannot always accommodate the treatment schedule,
with this in mind, a number of patients (4), chose to travel with
relatives or friends in their transport.
The overall costs to the patient are significantly higher in the
group treated in the secondary care setting. A number of patients
in this particular group commented on having to cancel engagements
for a full day. Older less mobile patients also required the
assistance of family members to accompany them to the hospital for
treatment.
Conclusions
This study has shown that PDT can be delivered in a community
setting and provides a viable alternative therapy for patients with
non-melanoma skin cancer who may be unable to attend the hospital
for treatment, in particular patients who live in rural
communities. The Xenon-arc PDT light source is easily portable. PDT
trained nurses can deliver the service efficiently and cost
effectively both in hospital and in the community.
The majority of patients suffering from Bowen’s disease and
superficial BCCs are over 65 years of age. The average age of
patient included in the study was 71 years. This is an age group
who may have co-morbidity and difficulty in travelling the long
distances needed to attend hospital appointments. PDT was well
tolerated in all patients included in this study. The treatment
received by patients was identical in both settings, and carried
out by the same trained staff. It is not surprising therefore to
find similar outcomes and cure rates in both groups. No significant
adverse events were observed, apart from mild discomfort during
irradiation. It is practice in some departments to administer local
anaesthesia prior to commencing PDT, this could be achieved in both
primary and secondary care by trained nurses where indicated. There
is limited data available regarding the safety and intermediate and
long-term side-effects of PDT. However, several authors have
supported its safety in the short term and experience from this
study suggests that PDT is safe and free from risk of serious or
major adverse events [9-11]. Although a number of patients reported
some discomfort associated with the application of 5-ALA or during
irradiation of the lesion, the therapy was well tolerated.
Ramrakha-Jones and Herd [8] found that PDT was one of the most
expensive methods of treating Bowen’s disease, but their cost
minimisation study looked at PDT that was delivered only in a
secondary care setting. The overall costs of community/primary care
based PDT are lower than those in secondary care in cases where the
overhead cost in secondary care is higher.
The cost to the patient is higher when they receive PDT in a
secondary care setting. This study has confirmed that patients
prefer treatment to be delivered nearer to their homes. The
efficiency of nursing time could be improved by using newer PDT
light sources, i.e. LED light sources are now available which can
treat multiple lesions with shorter treatment times. We estimate
that this would allow a nurse to treat up to five patients in a day
in a community setting, provided patients could be grouped into
convenient geographical areas.
References
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3 Stables GI, Stringer MR, Robinson DJ,
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957-60.
4 Morton CA, Whitehurst C, McColl JH, et al.
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