Biomedical Engineering Reference
In-Depth Information
European countries for the treatment of BD, using a protocol
with dosimetry as with MAL-PDT for AK (red LED light
source 634 ± 3 nm, 37 J/cm
2
, 50 mW/cm
2
), but with two treat-
ments 7 days apart, repeated at 3 months, if required (130).
Invasive SCC treated with ALA-PDT has been described in
three open-label studies with initial complete response rates of
54-100% for superfi cial lesions, but with recurrence rates of up
to 69% (mean 24%, 12 of 49, after 3-47 months) and a clearance
rate of only 40% (4 of 10) of nodular SCCs after 12-36 months
(131-133). In 2008, Calzavara-Pinton et al. treated 112 biopsy-
proven lesions of BD and SCC in 55 patients with MAL-PDT
using the red LED with the settings described above. After
3 months, the overall complete response was 73.2% and 53.6%,
respectively, at 2 years (134). Cell atypia was a statistically
sig nifi cant independent predictor of the treatment outcome
at 3 months. Therefore, the high effi cacy of topical PDT for
SCC-in situ suggests that depth of therapeutic effect is the limit-
ing factor for PDT in invasive SCC. Although topical PDT has
shown effi cacy, in view of its metastatic potential, topical PDT
cannot be currently recommended for the treatment of invasive
SCC (135,136).
(200-300 J/cm
2
at 150 mW/cm
2
) of a 633-nm laser irradiation
combined with 20% ALA in a cream base applied under occlu-
sion for either 4-6 hours or 18-24 hours (142). After 6 months
of a single treatment, they found complete clearance in 94 of
95 (99%) sBCC with 4- to 6-hour ALA, and in 93 of 98 (94%)
sBCCs with 18- to 24-hour ALA. There was no improvement
going from 200 to 300 J/cm
2
, which is consistent with the
sigmoidal shape of the response versus light dose curve.
At 3 years, recurrences were about 14% and the authors found
that retreatment of recurrences had about the same effi cacy as
did initial treatments.
Several trials in Europe, USA, and Australia have been per-
formed to investigate the effi cacy and safety of MAL-PDT for
the treatment of both sBCC and nBCC. Initial effi cacy is con-
sistently high, with clearance rates at 3 months after MAL-
PDT ranging from 80% (in diffi cult-to-treat cases, recurrent
or large lesions, or H-zone lesions) (143,144) to 97% in pri-
mary sBCC. In terms of long-term responses as nearly two-
thirds of all recurrent BCC lesions appear in the fi rst 3 years
after treatment (145,146). A 5-year follow-up of a randomized
trial (147) showed that recurrence with MAL-PDT (one PDT
treatment session only, retreatment after 3 months with two
sessions 7 days apart if required vs. double freeze-thaw cycle
also repeated after 3 months if necessary) is comparable with
cryotherapy (22% for MAL-PDT vs. 20% for cryotherapy at 60
months). However, more patients had an excellent outcome
with MAL-PDT (60% vs. 16% with cryotherapy).
Another clinical study by Szeimies and colleagues (148)
compared MAL-PDT (one cycle of two treatment sessions,
7 days apart, retreatment after 3 months with a second cycle if
required) and surgery in sBCC. Three months after last treat-
ment, the effi cacy of MAL-PDT was similar to that of surgery:
92.2% showed complete clearance at 3 months with MAL-
PDT versus 99.2% with surgery. However, at 12 months, 9.3%
of lesions recurred with MAL-PDT compared with none with
surgery. Cosmetic outcome was superior for MAL-PDT at all
time points, with 94.1% lesions treated with MAL-PDT having
an excellent or good cosmetic result compared with 59.8%
with surgery.
In diffi cult-to-treat populations, that is, large lesions, in the
H-zone, or in patients at a high risk for surgical complications,
Vinciullo et al. (149) treated 95 patients having 148 BCC
lesions (superfi cial, nodular or mixed superfi cial, and nodular)
with MAL-PDT (3-hour occlusion, 570-670 nm, 75 J/cm
2
,
50-200 mW/cm
2
) and achieved an estimated lesion complete
response rate of 90% at 3 months, 84% at 12 months, and 78%
at 24 months. Overall cosmetic outcome was rated as excellent
or good in 79% and 84% of the patients at 12 and 24 months,
respectively. Therefore, MAL-PDT does show good effi cacy
and is an attractive option when surgery would be inappropri-
ate or the patient wants to maintain normal skin appearance.
superficial basal cell carcinoma
BCCs are locally aggressive tumors that very rarely metastasize
and can be divided into three major groups: superfi cial, nodu-
lar, and infi ltrating morpheaform lesions. sBCC usually differs
from the other subtypes as it tends to appear at a younger
age, frequently occurs on the trunk, limbs, and neck and often
is multiple (137). A large number of treatment modalities
exist, including surgical techniques [excisional surgery, curet-
tage, and electrocautery, Mohs micrographic surgery (MMS),
cryosurgery], immune response modifi ers, cytotoxic agents,
and PDT. Table 10.3 shows the main clinical studies of topical
ALA- and MAL-PDT in sBCC.
In 1990, Kennedy et al. (138) were the fi rst to report a 79%
complete response rate at 3 months for 300 cases of sBCC
treated with ALA-PDT (3-6 hours application of 20% ALA
followed by fi ltered red light, 600+ nm). In 2001, Morton and
colleagues (139) treated 98 large or multiple sBCCs with ALA-
PDT and noted an 89% clearance rate after one or more treat-
ments. In another study by Clark et al. (140), patients were
treated up to four times with ALA applied for 6 hours followed
by irradiation with red lamps (570-720 nm), or a 630 nm
diode laser with a light dose of 125 J/cm
2
and found a 97%
clearance for sBCC. The number of treatments increased with
lesion diameter and the recurrence rate was 4.8% with a
median follow-up of 55 weeks. A comparison study by Wang
et al. (141) with ALA-PDT and cryotherapy (6-hour applica-
tion of ALA followed by illumination with a 635-nm dye laser;
60 J/cm
2
) for the treatment of sBCC and nodular BCC (nBCC)
noted no signifi cant difference in effi cacy between the two
groups. However, ALA-PDT was associated with fewer adverse
events, faster healing times, and better cosmetic results.
It should be noted that lesions were followed clinically and
biopsied at 3 months; they were re-treated on clinical grounds
or for histopathologic tumor and biopsied again at 12 months.
They found that despite only 5% of the ALA-PDT-treated
sBCC were clinical failures at 12 months, an additional 20% of
the treatment sites that were clinically clear had residual BCCs
on biopsy. Blume and colleagues used higher light doses
nodular basal cell carcinoma
Clinical results for nBCC using ALA-PDT varied more mark-
edly than those obtained for sBCC, with clearance rates rang-
ing from 64% to 92% (150). This difference might be due to
inadequate penetration of ALA into the deeper portions of the
skin and the malignancy (142), therefore, several strategies
have been studied to enhance effectiveness. One approach is to
debulk the lesion before PDT. Thissen and colleagues (151)
