Biomedical Engineering Reference
In-Depth Information
ALA-PDT is discussed in a separate section of this chapter.
However, a small study by Kim et al. (87) documented the use
of ALA-IPL for the treatment of AKs exclusively. Twelve facial
AK lesions in seven patients were treated with one session of
ALA-PDT. At 12 weeks follow-up, 50% of lesions cleared. This
clearance rate is markedly lower than reported averages, but it
is diffi cult to formulate sound conclusions based on the small
sample size.
Solid organ transplant recipients (OTRs) suffer from a
10- to 250-fold increase in AKs due to their ongoing immuno-
suppressive therapy (98). In addition, the precancerous and
cancerous lesions developing in the OTR population are often
more aggressive (98), requiring frequent and ongoing cancer
surveillance. PDT, a safe and effective treatment option for pre-
cancerous and malignant lesions, offered a new treatment
modality for controlling AKs and NMSCs in the OTR popula-
tion. Dragieva et al. assessed the response of AK in 17 trans-
plant recipients, each with two suitable sites, in a randomized,
placebo-controlled, double-blind study (99). Two MAL-PDT
treatments 7 days apart were compared with placebo-PDT.
At 4 months, there was lesion clearing in 13 of 17 sites with a
partial response in three while there was no reduction in size or
number of lesions in the sites treated by placebo-PDT. A ran-
domized intrapatient comparative study of 5-FU cream,
applied twice daily for 3 weeks, and topical MAL-PDT, two
treatments 7 days apart, in eight OTRs demonstrated that at
3 and 6 months after completion of treatment, PDT was more
effective than 5-FU in achieving complete resolution (100).
Eight of nine lesional areas cleared with PDT (Clearance rate
(CR) 89%, 95% CI: 0.52-0.99), compared with one of nine
lesional areas treated with 5-FU (CR 11%, 95% CI: 0.003-
0.48) (
P
= 0.02). In this study, a noncoherent red light source
(633 ± 15 nm; Paterson PDT Omnilux, Phototherapeutics Ltd,
Altrincham, UK) with an irradiance of 80 mW/cm
2
, and a total
dose of 75 J/cm
2
was applied to illuminate the treatment area
after 3-hour MAL incubation. Although initial response rates
of AKs following PDT were comparable in the OTR patient
population and normal controls (101), longer-term follow-up
demonstrated statistically signifi cant decreases in clearance
rates in the OTR population. In addition, SCC of the dorsal
hands and forearms were not prevented in OTRs in a 2-year
follow-up study, although there was a trend toward decreased
keratotic regions in the areas treated (102). PDT may still be a
viable treatment option in this population, but it may require
adjustments to typical treatment protocols, including increased
frequency of PDT sessions (101) and use of longer wavelengths
(red light) for deeper skin penetration (102).
Finally, multiple AKs, particularly those that develop within
the context of the fi eld of cancerization (103) with (pre-) neo-
plastic processes at multiple sites, frequently challenge our
clinical routine. In these patients, PDT appears to be very
effective, with a patient complete response rates varying from
82% to 68% (92,91,104) and generally well tolerated. A recent
randomized study by Serra-Guillen (105) compared tolerance
and satisfaction in the treatment of AK of the face and scalp
between 5% imiquimod cream and MAL-PDT. Among 58
patients included, there was a signifi cantly greater percentage
of patients very satisfi ed with the MAL-PDT treatment than in
the imiquimod group (93% in MAL-PDT vs. 62% in imiqui-
mod). Although the percentage of patients with good toler-
ance to the MAL-PDT was higher (38% for PDT vs. 21% for
imiquimod), the differences were not statistically signifi cant.
A randomized split-area study conducted by Palm and
Goldman compared the use of red versus blue light sources in
the treatment of AKs and photodamage in 18 patients with AKs
using MAL-PDT with 60-minute incubation. All patients
received illumination with PDLs and/or IPL, followed by split-
area treatment of either blue or red light. No statistically signifi -
cant differences in signs of photodamage and in improvement
treatment results of mal-pdt for ak
s
Three randomized comparison/control studies of MAL-PDT
using the same protocol (MAL 3 hours, 570-670 nm, 75 J/cm
2
,
50-250 mW/cm
2
) cleared 69% of predominantly thin and
moderately thick AKs of the face or scalp after a single treat-
ment (90), increasing to 89-91% when two treatments 7 days
apart were performed (13,91). In comparison, cryotherapy
cleared 68% and 75% (90,91) in two of these studies, with pla-
cebo responses of 30-38% (92,91). Superior cosmetic response
was observed in the MAL-PDT group in both studies that
compared PDT with cryotherapy (90,91).
A large randomized intraindividual study of 1501 face/scalp
AKs in 119 patients compared MAL-PDT (3-hour application)
using routine initial double therapy 7 days apart with double
freeze-thaw cryotherapy, repeating treatments at 3 months if
required (93). In this study, Morton et al. used red LED light
source (634 ± 3 nm, 37 J/cm
2
, 50 mW/cm
2
). PDT resulted in a
signifi cantly higher cure rate than cryotherapy (87% vs. 76%),
after initial cycle of treatments; however, fi nal outcome after all
nonresponders were retreated was equivalent. PDT also exhib-
ited signifi cantly superior cosmesis and overall subject prefer-
ence (effi cacy and skin discomfort).
It should be noted that a multicenter intraindividual ran-
domized trial comparing MAL-PDT versus cryotherapy for
multiple AKs on the extremities demonstrated inferior effi cacy
with PDT, with clearance of 78% of lesions at 6 months com-
pared with 88% for cryotherapy (94). The same red LED light
source and settings described above were used in this study, but
one single treatment was performed, to be repeated 3 months
later if complete response was not achieved, which might help
explain the different results found for facial/neck AKs. Besides,
AK on the extremities may also be modestly more resistant to
this treatment, according to results of previous smaller studies
of topical ALA-PDT (95,96). One possible explanation for an
increased resistance of AK of the extremities would be the lack
of pilosebaceous units in these areas, which are important to a
better absorption of prodrug and so to a better response. How-
ever, regarding cosmetic outcome in terms of both investigator
assessment and patient preference, MAL-PDT was superior to
cryotherapy. Patients also confi rmed their general preference
for MAL-PDT as a therapeutic option.
Using the same LED and MAL dosing parameters as above,
Tarstedt et al. (97) found that for thin lesions a single treat-
ment with MAL-PDT, repeated after 3 months in cases in
which lesions remained, was equally as effective (93% with
single MAL-PDT vs. 89% with double treatment) as using two
treatments, 7 days apart. However, for thicker lesions, they
found that clearance rates were greater after double treatment
(84% vs. 70% with single treatment). After this study, most
countries in Europe revised their MAL-PDT license in AK and
started to recommend an initial single treatment for thin AK,
with repeat after 3 months if necessary.
