Ac a De m Vene eol 96
CLINICAL REPORT
Ac a De m Vene eol 2016; 96: 241–244
© 2016 The Au ho s. doi: 10.2340/00015555-2205
Jou nal Compila ion © 2016 Ac a De ma o-Vene eologica. ISSN 0001-5555
Dayligh -media ed pho odynamic he apy (DL-PDT) is
conside ed as e ec i e as con en ional PDT using a i i-
cial ligh (ligh -emi ing diode (LED)-PDT) o ea men
o ac inic ke a oses (AK). This andomized p ospec i e
non-sponso ed s udy assessed he cos -e ec i eness o
DL-PDT compa ed wi h LED-PDT. Se en y pa ien s
wi h 210 AKs we e andomized o DL-PDT o LED-PDT
g oups. E ec i eness was assessed a 6 mon hs. The cos s
included socie al cos s and p i a e cos s, including he
ime pa ien s spen in ea men . Resul s a e p esen ed
as inc emen al cos -e ec i eness a io (ICER). The o al
cos s pe pa ien we e signi ican ly lowe o DL-PDT
(€132) compa ed wi h LED-PDT (€170), gi ing a cos
sa ing o €38 (p = 0.022). The es ima ed p obabili ies o
pa ien s’ comple e esponse we e 0.429 o DL-PDT and
0.686 o LED-PDT; a di e ence in p obabili y o being
healed o 0.257. ICER showed a mone a y gain o €147
pe uni o e ec i eness los . DL-PDT is less cos ly and
less e ec i e han LED-PDT. In e ms o cos -e ec i e-
ness analysis, DL-PDT p o ides lowe alue o money
compa ed wi h LED-PDT. Key wo ds: ac inic ke a oses;
cos -e ec i eness; dayligh -pho odynamic he apy.
Accep ed Aug 4, 2015; Epub ahead o p in Aug 10, 2015
Ac a De m Vene eol 2016; 96: 241–244.
Noo a Nei aanmäki-Pe u, Depa men o De ma ology
and Alle gology, Helsinki Uni e si y Hospi al, Box 160
Meilahden ie 2, FIN-00029 Helsinki, Finland. E-mail:
[email p o ec ed]
Ac inic ke a oses (AK) a e p ecu so s wi h po en ial o
de elop in o me as a ic squamous cell ca cinoma (SCC)
(1). High incidence a es o AKs aise a signi ican
economic issue. The p e alence o AK is es ima ed o
be app oxima ely 50% in Aus alia and 11–34% in he
No he n hemisphe e, wi h highe p e alence among
elde ly subjec s (2–4). The o al annual di ec cos s o
AKs we e 18 million Eu os (€) in Sweden in 2011 and
1.2 billion USD in he US in 2004 (5, 6).
The e a e se e al opical ea men op ions o AKs
(7, 8). Pho odynamic he apy (PDT) is a ecommended
ea men op ion (9–11). A no el app oach, using day-
ligh (DL-PDT) in he ea men o AKs is conside ed
o be as e ec i e as ea men wi h con en ional PDT
using a i icial ligh (ligh -emi ing diode (LED)-PDT)
(12, 13). The use o DL-PDT is hough o be less cos ly
due o sho e isi ing imes a he clinics (13, 14). To
ou knowledge, he cos -e ec i eness o DL-PDT o
he ea men o AK has no been s udied p e iously.
This s udy was a p ospec i e andomized non-spon-
so ed ial o assess he cos -e ec i eness o DL-PDT
compa ed wi h LED-PDT in he ea men o AKs.
MATERIALS AND METHODS
The s udy p o ocol ollowed he Decla a ion o Helsinki and
was app o ed by he local e hics commi ee. All pa icipan s
p o ided in o med consen . Fo ull de ails, see Appendix S11.
All pa ien s who ul illed he inclusion c i e ia we e sequen-
ially ec ui ed om he Depa men o De ma ology, Päijä -
Häme Cen al Hospi al be ween 2011 and 2013. Inclusion
c i e ia included a minimum o 3 clinically clea ly de ec able
AKs on acial o scalp a eas. Exclusion c i e ia a e de ailed in
Appendix S11.
Pa ien s we e andomized o ecei e ei he DL-PDT o LED-
PDT. Be o e ea men s AK lesions we e pho og aphed, coun ed
and classi ied in o g ades I–III (16).Th ee clea ly de ec able
a ge lesions pe pa ien we e chosen o he s udy ollow-up.
I pa ien s had mo e han 3 lesions, all lesions we e ea ed
acco ding o he andomiza ion. G ade I lesions we e ea ed
once and g ades II–III lesions wice. The ea men p ocedu e
is de ailed in Appendix S11.
Response was e alua ed clinically (pa ien comple e e-
sponse, 3 a ge lesions clea ed) a 6 mon hs. E ec i eness was
de ined by he le el as he p obabili y o pa ien ’s comple e
esponse a 6 mon hs.
Cos s included socie al cos s (including he wo king ime
o he nu se and doc o , ea men oom en , medica ion and
equipmen ) and pa ien s’ cos s (including ea men ime and
a el cos s). The analysis adop ed a socie al pe spec i e,
including bo h heal hca e and pa ien s’ cos s (Table I). The
cos s o con ol isi s o u he ea men s we e no included.
Cos -e ec i eness analysis (CEA) was pe o med using DL-
PDT and LED-PDT as he in e en ion and con ol ea men s,
espec i ely, gene a ing he inc emen al cos -e ec i eness
a io (ICER). Fo a de ailed desc ip ion o he me hod, see
Appendix S11.
Pho odynamic The apy o Ac inic Ke a oses: A Randomized
P ospec i e Non-sponso ed Cos -e ec i eness S udy o Dayligh -
media ed T ea men Compa ed wi h Ligh -emi ing Diode T ea men
Noo a NEITTAANMÄKI-PERTTU1,2, Ma i GRÖNROOS2, Toni T. KARPPINEN2, E na SNELLMAN3 and Pekka RISSANEN4
Depa men s o De ma ology and Alle gology, 1Helsinki Uni e si y and Helsinki Uni e si y Hospi al, Helsinki, 2Päijä -Häme Cen al Hospi al, Päijä -
Häme, 3Depa men o De ma ology, Tampe e Uni e si y and Tampe e Uni e si y Hospi al, and 4School o Heal h Sciences (Heal h Economics), Tampe e
Uni e si y, Tampe e, Finland
1h p://www.medicaljou nals.se/ac a/con en /?doi=10.2340/00015555-2205
242 N. Nei aanmäki-Pe u e al.
RESULTS
Pa ien s
O he 73 andomized pa ien s 3 we e excluded; one due
o an un ela ed dea h, one o diagnosed SCC on he
s udied a ea be o e ea men , and one o se e e di use
pho o-damage ha hinde ed he coun o AKs (Fig S1
1
).
A o al o 70 pa ien s comple ed he s udy, 39 men and
31 women, age ange 59–93 yea s (mean 76 yea s). Eigh
pa ien s had anamnes ic skin pho o- ype I, 25 pho o- ype
II, 34 pho o- ype III, and 3 pho o- ype IV. Fo y-six pa-
ien s had ea lie ecei ed ea men o hei AKs and 3
o ca cinoma in si u. Six had had ope a ions o SCC,
18 o basal cell ca cinoma (BCC), 1 o melanoma and
one o e ucous ca cinoma, o which 2 BCCs, one SCC
and e ucous ca cinoma we e in he s udied skin a eas.
Twen y- ou pa ien s had p e iously ecei ed c yosu -
ge y, 8 DL-PDT and 11 LED-PDT o AKs on he s udied
a eas. In addi ion, 5 pa ien s had ecei ed LED-PDT, 23
c yosu ge y, 1 imiquimod, 1 diclo enac and 1 opical
e inoid ea men o AKs in o he skin a eas. None o
he pa ien s had ecei ed bo h DL-PDT and LED-PDT.
The e was a wash-ou pe iod o a leas 6 mon hs om
p e ious ea men s o he s udied a eas.
Thi y- i e pa ien s ecei ed DL-PDT and 35 ecei-
ed LED-PDT. Se en pa ien s in bo h g oups ecei ed
2 ea men s o hicke lesions 7–23 days apa (mean
12 days) and he es ecei ed one ea men session.
The mean ime o dayligh -exposu e was 161 min
( ange 120–480 min). Pa ien s did no isi o con ac
he hospi al be ween ea men s and con ol isi s.
Th ee a ge lesions pe pa ien we e included in he
s udy; hus, he numbe o lesions s udied was 210, o
whom 105 (92 g ade I, 13 g ade II–III) we e ea ed wi h
DL-PDT and 105 (93 g ade I and 12 g ade II–III) wi h
LED-PDT (p = 0.46). Pa ien comple e esponse a es (3/3
lesions clea ed) we e 15 o 35 (42.9%) wi h DL-PDT and
24 o 35 (68.6%) wi h LED-PDT (p = 0.030) (Fig S1
1
).
To be e compa e ou esul s wi h p e ious DL-PDT
s udies, we also conduc ed pe lesion clea ance analysis.
A 6 mon hs LED-PDT clea ed 94 o 105 (89.2%) and
DL-PDT 76 o 105 (72.4%) lesions (p = 0.0025). In
he LED-PDT g oup 93 g ade I AKs ecei ing 1 and
12 g ade II–III AKs 2 ea men s showed 88.2% and
100% comple e clea ance, espec i ely (p = 0.36). In
he DL-PDT g oup 92 g ade I AKs ecei ed 1 ea men
and 13 g ade II–III AKs 2 ea men s wi h 73.9% and
61.5% clea ance a es (p = 0.34).
Cos s
The impu ed mean o al cos s pe pa ien (1–2 ea -
men s) we e €132 (95% con idence in e al (CI) 111.3–
152.6) o DL-PDT and €170 (95% CI 126.0–213.5)
o LED-PDT, esul ing in inc emen al cos s sa ings
o –€38 (p = 0.022) (Table I).
Cos -e ec i eness
The p obabili ies o pa ien s’ comple e esponse we e
0.429 (95% CI 0.414–0.443) o DL-PDT and 0.686
(95% CI 0.674–0.698) o LED-PDT, hus yielding a loss
in he p obabili y o being healed o 0.257. The ICER
e ealed a mone a y gain o €147 pe uni o e ec i eness
los (Table II). The cos -e ec i eness (CE)-plane showed
ha app oxima ely 96% o he boo s apped eplica da a
yielded a esul ha lies in he sou h-wes e n pa o he
plane, indica ing ha DL-PDT p o ided a lowe alue
o money compa ed wi h LED-PDT (Fig S2
1
).
Addi ional da a analysis
When di iding he mean cos pe pa ien wi h he
es ima ed p obabili y o pa ien ’s
comple e esponse, he cos s pe
comple e esponde s we e calcula-
ed as €308 o DL-PDT and €248
o LED-PDT (p = 0.004).
DL-PDT equi ed signi ican ly
less o he nu ses’ ime (median 51
s. 78 min pe ea men , p = 0.003)
and less o he pa ien s’ ea men
ime (median 194.5 s. 271 min,
p < 0.0001) compa ed wi h LED-
PDT.
As measu ed wi h he isual analo-
gue scale (VAS, ange 0–10) du ing
and a e he ea men s un il he pain
had anished, DL-PDT was signi-
ican ly less pain ul, wi h a mean
maximal pain alue o 1.53 ( ange
0.1–6.0) compa ed wi h LED-PDT
4.36 ( ange 0.3–8.4), p < 0.001).
Table I. Cos i ems, uni cos and mean o al cos s o dayligh -media ed pho odynamic
he apy (DL-PDT) compa ed wi h ligh -emi ing diode PDT (LED-PDT) o ea men
o ac inic ke a oses (AK) (p = 0.022)
Cos i em Uni cos s
DL-PDT, €
n = 35a
Mean ± SD
LED-PDT, €
n = 35a
Mean ± SD
Socie al cos s
Nu ses’ ime wi h he pa ien €19/h 17.1 ± 4.3 24.9 ± 6.6
Doc o s’ ime ( esiden ) o he ea men €30.2/h 9.0 ± 3.0 9.0 ± 3.0
T ea men oom en €1.5/h 1.4 ± 0.3 2.0 ± 0.5
Pho osensi ize (me hylaminolae ulina e) €163/g 37.2 ± 26.3 50.4 ± 31.8
Anaes he ic €0.3/ml 0.25 ± 0.56 0.23 ± 0.53
Sunsc een €0.1/ml 1.6 ± 0.53 –
Occlusion memb ane €0.3/20 cm – 0.35 ± 0.12
LED ligh €0.14/illumina ion – 0.16 ± 0.05
Hospi aliza ion €385/nigh b–11
Pa ien s’ cos s
Pa ien s’ (pensione ) ime used o he ea men €8.6/h 40.4 ± 23.0 49.6 ± 21.8
Pa ien s’ a el cos s €0.45/km 25.0 ± 22.1 22.1 ± 30.9
Mean o al cos s 132 ± 62.3 170 ± 132.0
a28/35 pa ien s ecei ed one ea men session, 7/35 pa ien s ecei ed 2 ea men s o g ade II–III
AKs. bOnly 1 pa ien spen a nigh a he hospi al due o pain in he ea men a ea a e LED-PDT.
Ac a De m Vene eol 96
243
Cos -e ec i eness o DL-PDT and LED-PDT
DISCUSSION
The esul s o his s udy show ha DL-PDT is less
cos ly, bu also less e ec i e, han LED-PDT. DL-
PDT was associa ed wi h an inc emen al cos sa ing
o €147 and a dec emen al p obabili y o being healed
o –0.257. Thus, DL-PDT p o ides a lowe alue o
money compa ed wi h LED-PDT.
The cos -e ec i eness o LED-PDT compa ed wi h
o he ea men s o AK has been e alua ed in se e al s u-
dies. A limi a ion o many o hese s udies compa ed wi h
ou p ospec i e s udy using accu a e cos s is ha hey use
es ima ed cos s; some o he s udies included only he cos
o he opical d ug. To ou knowledge he e ha e been no
cos -e ec i eness e alua ions o DL-PDT. The simula ed
cos s pe comple e esponde we e €379 o MAL-PDT
and €363 o c yo he apy, including he cos o yea ly
e- ea men s, and aluing he cosme ic ou come. The
inc emen al cos pe ex a comple e esponde was €401,
wi h MAL-PDT being mo e expensi e (18). When LED-
PDT was compa ed wi h imiquimod using a decision- ee
model es ima ing quali y-adjus ed li e yea s (QALYs) and
ea men cos s, i was implied ha imiquimod migh be
mo e cos -e ec i e (19). A ecen p ospec i e head- o-
head s udy ound ha MAL-PDT was mo e cos -e ec i e
compa ed wi h diclo enac + hyalu onic acid gel (DHA),
wi h he cos s pe comple e esponde being €566.7 and
€1,026.2 o MAL-PDT and €595.2 and €2,295.2 o DHA
a 3 and 12 mon hs, espec i ely
(20). Ou s udy showed
ha he cos s pe comple e esponde we e €308 o DL-
PDT and €248 o LED-PDT a 6 mon hs. A limi a ion o
ou s udy is ha we did no include he cos s o u he e-
a men s o he quali y o li e analysis (QALY), and hus he
numbe s a e no di ec ly compa able wi h p e ious da a.
PDT s udies a ely epo esponse a es a he pa ien
le el. In he I alian s udy, he pa ien comple e esponse
a e o LED-PDT was 68.4% a 3 mon hs and 55.2% a
1 yea (19). In ano he s udy, MAL-PDT was supe io o
a placebo, wi h a pa ien comple e esponse o 59.2% s.
14.9% a 3 mon hs (21). Ou esul s a e in conco dance
wi h hese indings, showing a 68.6% pa ien comple e
esponse a e o LED-PDT a 6 mon hs. Ou pa ien
comple e esponse a e o DL-PDT was 42.9%. To
ou knowledge, he pa ien comple e esponse o DL-
PDT has no been epo ed ea lie . As pa ien comple e
esponse is a majo indica o o he need o u he
ea men s and u he cos s, u u e esea ch should
ocus mo e a en ion on his subjec .
The majo i y o PDT s udies epo lesion clea ance
a es anging om 71% o 92% o LED-PDT, and om
75.9% o 79.5% o DL-PDT (10, 13, 14, 22, 23). Ou
esul s show equal clea ance a es o LED-PDT (89.2%),
bu sligh ly lowe clea ance a es o DL-PDT (72.4%).
The sligh ly lowe e icacy a es o DL-PDT could be
explained by a longe ollow-up pe iod (6 mon hs) han
in he p e ious s udies epo ing 3-mon h clea ance a es.
A ew ac s migh ha e a ec ed ou DL-PDT e ec-
i eness esul s
2
.
Despi e i s highe e icacy, LED-PDT migh no be
an a ac i e op ion o pa ien s, as he use o DL-PDT
esul s in signi ican ly less pain and ime spen a he
clinic. Thus, we s ill p e e he use o DL-PDT o e
he con en ional ea men du ing he summe mon hs.
Wi h i s sho isi ime, DL-PDT can be implemen ed
in p i a e p ac ices, which could educe he bu den
on public clinics. A u he CEA analysis o DL-PDT
should be conduc ed including QALYs and pa ien p e-
e ence. Fu he mo e, he cos -e ec i eness o newe
Table II. Inc emen al cos -e ec i eness a io (ICER)
E ec i eness (E) Cos s (C) ICER
P obabili y
o comple e
esponse
Inc emen al
e ec i eness
Pe
pa ien
€
Inc e-
men al
cos
€/P obabili y
o comple e
esponse
DL-PDT 0.429 132
LED-PDT 0.686 –0.257 170 –38 147
DL-PDT: dayligh -media ed pho odynamic he apy; LED-PDT: ligh -emi ing
diode pho odynamic he apy.
2Me eo ological s udies ha e shown ha DL-PDT can be implemen ed in
Reykja ik (loca ed in he same la i ude (64°N) wi h Finland) un il he middle
o Sep embe (24). In he i s 2 yea s we con inued ea men s un il ea ly
Oc obe , which in luenced he esponse a es. O he 14 pa ien s ea ed in la e
Sep embe o ea ly Oc obe only 16.7% (1/6) in he DL-PDT g oup and 87.5%
(7/8) in he LED-PDT g oup we e comple ely clea ed. Thus, he ea men
should be limi ed o he summe mon hs in no he n coun ies. Howe e ,
he mos e ec i e ligh -dose needed o DL-PDT emains unclea . We did
no use ligh -dosime e s o DL-PDT and hus accu a e ligh doses a e no
a ailable. We used a di e en sunsc een (ACO Sun Kids High P o ec ion
Sun Sp ay® SPF 30, ACO) om ha used in p e ious s udies (14). Howe e ,
he abso p ion spec um only minimally o e lapped he blue ligh egion and
hus was assumed no o a ec ea men ou come. A 0.25-mm hick laye o
MAL c eam has been app o ed as su icien o DL-PDT, esul ing in 74%
lesion comple e clea ance (25). To ou knowledge he e icacy o <1-mm
laye pho osensi ize has no been s udied o LED-PDT. Thus, in ou s udy,
he DL-PDT g oup ecei ed a hinne laye o MAL c eam (0.25 mm) han
he LED-PDT g oup (1 mm), which educed he cos s o DL-PDT, bu also
may ha e a ec ed he esponse a e. In LED-PDT we used he s anda dized
p o ocol o a 1-mm hick laye o he pho osensi ize unde 3 h occlusion,
while no occlusion was used in DL-PDT. This esul s in highe amoun s o
p o opo phy in IX (PpIX) in he issues o he LED-g oup han in he DL-
g oup; in he la e PpIX is ac i a ed while de eloping (13). A la ge ial
e alua ing di e en hicknesses o MAL c eam in LED-PDT is wa an ed.
The p esen s udy ound DL-PDT o be signi ican ly less pain ul compa ed
wi h LED-PDT. A limi a ion is ha his inding and pa ien p e e ence we e
no included in assessmen o QALYs and he CEA analysis. LED-PDT migh
no be an a ac i e op ion o pa ien s, as he use o DL-PDT signi ican ly
lowe s pain and ime spen a he clinic. An ea lie spli - ace s udy compa ing
LED-PDT and DL-PDT epo ed highe pa ien p e e ence o DL-PDT
(13). Fu he limi a ions o ou s udy include he lack o in es iga o -blinded
ou come e alua ion and assessmen o ad e se eac ions. We did no pe o m
skin biopsies o e i y AK diagnoses, and despi e he high accu acy o clinical
diagnoses his should be conside ed a limi a ion (26). To simpli y he ea men
p ocess o cos e alua ion we used a ea men me hod a ge ed o lesions.
Had we a ge ed he whole ield, he cos o he ea men would ha e been
highe and his may ha e a ec ed he CEA analysis. The esul s may no be
easily gene alized o he wo king age popula ion as i ocused on pensione s.
Ac a De m Vene eol 96
244 N. Nei aanmäki-Pe u e al.
low-concen a ion pho osensi ize s in DL-PDT needs
o be s udied (25, 27).
In conclusion, his s udy assessing he de ailed cos s
o DL-PDT and LED-PDT o ea men o AKs ound
ha , in e ms o CEA, DL-PDT p o ides a lowe alue
o money compa ed wi h LED-PDT.
ACKNOWLEDGEMENTS
We would like o hank esea ch nu se Ulla Oesch-Lää e i om
Päijä -Häme Cen al Hospi al o he dedica ion o his s udy.
The co esponding au ho ecei ed a esea ch g an om O ion
Pha mos Founda ion (no in ol ed in any o he p oduc s used in
he s udy) and om Founda ion o Clinical Chemis y Resea ch.
The au ho s decla e no con lic s o in e es .
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