Biomedical Engineering Reference
In-Depth Information
reported a clearance rate of 92% (22 of 24 tumors) after a
single cycle of ALA-PDT (noncoherent red light, 100 mW/cm
2
,
120 J/cm
2
) with debulking curettage performed three weeks
earlier. Another approach used to increase ALA within the
lesion was iontophoresis and the addition of dimethylsulfox-
ide (DMSO) or ethylenediaminetetraacetic acid (152,153).
Christensen and colleagues (154) demonstrated clearance of
91% BCC lesions (24 sBCC and 36 nBCC) at 3 months and
81% remained disease-free at 72 months with one or two ses-
sions of DMSO-supported ALA-PDT following curettage.
Topical MAL has shown superior tissue penetration over
ALA due to its decreased charge and increased lipophilicity
(155). Whether these properties make MAL more effi cacious
than ALA is unknown with only one small randomized study
by Kuijpers and colleagues (156) showing similar effectiveness
of MAL and ALA-PDT for nBCC.
Five phase III studies in which a total of 220 nBCCs were
treated (143,149,157-159) with MAL-PDT have demonstrated
signifi cant effi cacy with 3-month complete response rates of
73-94%. It should be noted that histologically controlled stud-
ies have confi rmed the reliability of effi cacy data (73% and
79%). Two studies by Horn et al. (117) and Vinciullo et al.
(149) examined the use of MAL-PDT in “diffi cult-to-treat”
and high-risk cases and still found 3-month response rates of
87% and 82% for nBCC, respectively. However, at 24 months
after treatment, Vinciullo found a lower sustained lesion clear-
ance rate of 67% for nodular lesions.
A comparison study of MAL-PDT versus surgery for nBCC
(159,160) has provided a 3-month response rate noninferior
to surgery (91% compared with 98% for surgery) and a
60-month recurrence rate of 14% compared with 4% with
surgery. However, estimated sustained lesion complete
response rates were 76% for MAL-PDT compared with 96%
for surgery. The authors concluded that a favorable cosmetic
outcome, with 82% rating as excellent or good versus 33% in
the surgery group, combined with moderately low 5-year
lesion recurrence with MAL-PDT supports a clinical role for
this modality of treatment for nBCC.
In 2009, Foley et al. (161) published favorable results for
nBCC (
source (red light), and dose has been developed for nBCC in
the countries where MAL-PDT is approved for this particular
condition, current evidence supports the use of MAL rather
than ALA for PDT of nBCC (163). Table 10.4 shows the main
clinical trials of topical ALA- and MAL-PDT in nBCC.
More recently, photodynamic diagnosis using MAL in con-
junction with a Wood's lamp examination has been reported
as an adjunctive to accentuate tumor margins before MMS
(164), showing a high degree of consistency between post-
MMS defect and fl uorescent examination size. Therefore, this
technique has the potential for increasing the effi ciency of
MMS, by decreasing the number of stages. It should be noted
that Tierney and colleagues (164) used a 13-hour preincuba-
tion time in order to maximize the signal-to-noise ratio of
tumor fl uorescence relative to background fl uorescence of
non-tumor-laden skin. Another study by Lee and colleagues
(165), using 20% ALA ointment 6 hours before MMS for
NMSC, failed to fi nd any effi cacy of photodynamic diagnosis
though; the authors concluded that many variables such as
tumor thickness, type of photosensitizer, incubation time
might affect the fl uorescence, therefore future large-scale stud-
ies are still needed.
Photorejuvenation
Definition of Photoaging
Photodamage is a marker of cumulative UV exposure and
senescent changes to the skin. Not only can the appearance be
concerning to the patient, but it can also lead to precancerous
conditions with the development of AKs (166). The character-
istic appearance of photodamaged skin includes sallow discol-
oration, inelasticity, rhytid formation, pigmentary alteration,
ecstatic vessels/telangiectasias, and textural alterations (45).
Global photodamage scales have been developed for scoring
the severity of skin involvement. Dover used a 5-point scale in
evaluating several categories of photodamage, including fi ne
surface lines, mottled pigmentation, sallowness, tactile rough-
ness, coarse wrinkling, and global photodamage (167). Work-
ing from this initial scale, others have added facial erythema,
telangiectasias, sebaceous gland hyperplasia, and facial AKs as
separate categories in the evaluation of photodamage (168,169).
5 mm in depth) from two randomized studies, show-
ing histologically verifi ed lesion complete response rates of
73% with MAL-PDT (two sessions, 7 days apart repeated after
3 months if necessary) versus 27% with placebo at 6 months
after last treatment. Although curettage was used to debulk
rather than remove the tumor, repeat curettage and infl amma-
tion associated with the debridement procedure could have
contributed to high response rate with the placebo-PDT.
Although thickness of nBCC has not specifi cally been assessed
in other trials, a retrospective study of MAL-PDT for nBCC
found recurrence rates of 7% and 14% for thin (<2 mm) and
thick (>2 mm) nBCC, respectively, at a median 35-month of
follow-up, suggesting that thin nBCC might be particularly
responsive to MAL-PDT (162).
In terms of cosmetic outcome, PDT in nBCC usually
achieves superior results compared with other modalities,
such as cryotherapy (141) and surgery (159), with 82-95%
(141,143,151,157,159,162) of patients rating as “excellent” or
“good.”
Since the penetration of MAL is higher than that of ALA and
a standardized protocol involving lesion preparation, light
≤
Light Sources in ALA- and MAL-PDT Photorejuvenation
Many of the same lasers and light sources effective in ALA- and
MAL-PDT for the treatment of AKs have the added benefi t of
inducing photorejunative effects on the skin. Chromophores
targeted during PDT treatment may include vessels, melanin,
and even collagen (168). Blue light only allows for a photo-
chemical effect in PDT with less tissue penetration than other
light sources, such as IPL and PDL. The latter sources pene-
trate deeply enough to target vessels, pigment, and collagen
(170). The choice of which light source to use ultimately
depends on such factors as the condition being treated, effi -
cacy, cost of use, and availability of equipment.
Treatment Results of ALA- and MAL-PDT
in Photorejuvenation
Studies relating to the treatment of photodamage with ALA-
and MAL-PDT are organized in the section below according to
the light source employed. A summary of these studies is pro-
vided in Table 10.5.
