Biomedical Engineering Reference
In-Depth Information
of AKs following MAL-PDT were observed between blue
light- and red light-treated sides. Additionally, side effects
were mild and did not differ between treatment sides (106).
occurring on the lower part of the legs (92) and is associated
with a small risk of progression (about 3%) to an invasive
SCC (97).
This condition has been widely proposed as an indication for
topical PDT with several studies confi rming the effi cacy of
ALA-PDT. Topical ALA-PDT clears, on average, 86-93% of
lesions of BD following one or two treatments (115). Three
small randomized trials using nonlicensed ALA formulations
and identical protocols demonstrated that PDT was equivalent
in effi cacy to cryotherapy (116), superior to 5-FU (117) and sig-
nifi cantly more effective when delivered narrowband red instead
of green light (118), possibly related to deeper tissue penetra-
tion. Table 10.2 provides a summary of peer-reviewed articles
on the use of ALA-PDT and MAL-PDT in BD treatment.
A large multicenter study has been completed by Morton
and colleagues comparing MAL-PDT with cryotherapy or
topical 5-FU (119). In this randomized placebo-controlled
study, 225 patients with 275 lesions had histologically con-
fi rmed intraepithelial SCC, with 111 lesions treated with two
MAL-PDT treatments, 7 days apart, with a repeat cycle after
3 months if necessary. Cryotherapy was performed as a single
freeze-thaw cycle to achieve an ice fi eld that persisted for at
least 20 seconds and 5-FU was topically applied once daily for
3 weeks. Both the treatment modalities were also repeated if
required. After 3 months, MAL-PDT achieved clearance of
93% in comparison with 86% and 83% for cryotherapy and
topical 5-FU, respectively. The remission rate after 12 months
was 80% with MAL-PDT versus 67% with cryotherapy
(
P
= 0.047) and 69% (
P
= 0.19) with 5-FU. At 24 months
following fi nal treatment lesion, clearance rates were 68% for
MAL-PDT, 60% for cryotherapy, and 59% for 5-FU (120).
Cosmetic outcome at 3 months was good or excellent for 94%
of patients from the PDT group in comparison with 66% for
the cryotherapy and 76% for 5-FU.
Data concerning long-term clearance are limited, but in one
retrospective study of 617 patients, Thestrup-Pedersen and
colleagues (121) found relapse rates (>5 years) of 34% for
cryotherapy, 19% for curettage, 14% for 5-FU, 6% for radio-
therapy, and 5% for surgery. With a 64-month recurrence rate
of 17% in BD as noted by Leman et al. (122) following ALA-
PDT, PDT, comparing with more established therapies, seems
to have an acceptable long-term effi cacy.
Topical PDT seems to be an especial option for the treat-
ment of large and multiple patches of BD (123). Morton et al.
found an initial clearance rate after ALA-PDT for 40 large,
20-55 mm diameter lesions after one to three treatments of
88% falling to 78% at 12 months.
Case reports and series have demonstrated a benefi cial use
of topical PDT to clear BD in unusual sites (nipple, subun-
gueal) (124-126) and in cases of poor healing settings (epider-
molysis bullosa and radiation dermatitis (127,128) as well.
Tolerability of MAL-PDT in BD was generally excellent and
superior to standard treatments in the study by Morton et al.
(129). Most patients experienced a certain degree of pain, but
it was less severe than that caused by cryotherapy, whereas
5-FU was associated with poor local tolerability, eczematous
reaction, ulceration, and erosion.
Topical PDT may represent a valuable treatment option for
BD as a tissue-sparing, noninvasive therapy with high effi cacy
and good tolerability. MAL-PDT has been approved in most
Combination Therapy for AK Treatment
Several small case studies have demonstrated a possible syner-
gistic effect of ALA-PDT with other treatment options for AKs.
Combination 5-FU cream with PDT was tested in a study by
Gilbert (107). Fifteen patients with multiple AKs completed a
fi ve-day course of nightly 5-FU cream to the face followed by
short-contact PDT activated by an IPL light source. A clearance
rate of 90% was observed at 1 year follow-up. Martin (108) per-
formed a split-area study with three patients treated with ALA-
PDT alone versus sequential therapy with 5-FU (7-10 days)
and short-contact ALA-PDT (1 hour ALA incubation followed
by blue light 417-432 nm illumination). At follow-up visit,
6 months after initial visit, the combined regimen showed
enhanced effi cacy in treating AK, suggesting synergistic effects
of 5-FU and ALA-PDT. Shaffelburg (109) conducted a split-
face study of 24 patients with multiple AKs, in which ALA-
PDT was performed on the entire face. A half of the face was
also randomized to receive additional subsequent treatment
with a 12-week regimen of imiquimod. Clearance rates at
12 months were superior on the combination treatment side,
with 89.9% complete lesion clearance compared with 74.5%
on the ALA-PDT treatment side alone.
nonmelanoma skin cancer
BCC is the most common malignant skin tumor in the
Caucasian population and is classifi ed together with SCC as
NMSC. It is estimated that NMSC affects at least 1-2% of the
population annually (110,111), with 0.9-1.2 million new cases
of NMSC diagnosed each year in the USA; of these 80% are
BCC and 16% are SCC (110). Risk factors to NMSC include
exposure to UV radiation, light complexion, male gender,
increasing age, immunosuppression, precancerous skin lesion,
and ionizing radiation (111,112).
Treatment of NMSC usually is based on clinical type, tumor
size, and location; and also other important factors should be
considered, such as maintaining close to normal skin appear-
ance, downtime, treatment compliance, therapeutic risks
related to comorbidities, and medications (anticoagulants,
immunosuppressive therapy). Apart from surgical excision,
which is the standard treatment for cutaneous SCC, other
treatment options exist, including curettage and electrocau-
tery, cryotherapy, radiotherapy, cytotoxic agents, and immu-
noresponse modifi ers.
PDT with methylaminolevulinate is an innovative treatment
modality that has been approved in Europe for the treatment
of superfi cial BCC (sBCC), nodular BCC (nBCC), AKs, and
BD (114). Herein, we revise the evidence for the effi cacy and
safety of PDT in the treatment of NMSC.
Figure 10.6A illustrates a case of basosquamous carcinoma
on the shoulder treated with ALA-PDT.
bowen
s disease
BD typically presents as an enlarging, erythematous plaque,
well demarcated with a crusted or scaling surface (111). This
epidermal dysplasia, histologically corresponding to SCC-in
situ, is particularly common in elderly patients, frequently
'
