COMMUNICATION AND BRIEF REPORT

The Effect of Photodynamic Therapy on Contiguous UntreatedTumor

HUMBERTO CABRERA, PHD,*† JORGE CASTRO, MD,‡ HILDA C. GRASSI, MSC,§

EFREN D. J. ANDRADES, MSC,§ AND SANTOS A. LOPEZ-RIVERA, PHD¶

The authors have indicated no significant interest with commercial supporters.

Photodynamic therapy (PDT) is an antitumor

method that uses a nontoxic photosensitizer

and visible light to produce cytotoxic reactive oxy-

gen species (ROS) that destroy malignant cells. It

has been increasingly used in the treatment of non-

melanoma skin cancers, particularly basal cell car-

cinoma (BCC), providing a high degree of tumor

regression and excellent aesthetic results. We report

the case of a patient with histopathologically pro-

ven superficial BCC in which regression of

untreated contiguous tumor was noted after PDT.

Case Report

PDT was administered to a 60-year-old woman

with histopathologically proven superficial BCC

near the nasal tip. Informed consent was obtained

from the patient according to the approved proto-

col of the institutional ethics committee, which

was in agreement with the guidelines of the 1975

Declaration of Helsinki. The patient reported no

prior personal history of skin cancer and subse-

quently consented to PDT at the Plastic Surgery

Unit of the Hospital Oncology Service, Instituto

Venezolano de los Seguros Sociales. The physician

observed the vital signs of the patient as well as

the response of the tumor to the treatment during

the first minutes; at 6, 24, and 48 hours; at the first

week; weekly for 8 weeks; and every 3 months for

1 year.

The photosensitizer used in this treatment was the

commercial chlorin derivative Photolon (Chlorine

e6-PVP, Scientific Pharmaceutical Center, RUE

Belmedpreparaty, Minsk, Belarus). The drug dose

was 1.7 mg/kg of body weight diluted in 200 mL

of saline solution injected intravenously slowly

over a 20-minute period; the drug–light application

interval was 3 hours. The light source used was

the diode laser (ML-662-SP, Milon Laser Ltd.,

Sain-Peterburg, Russia) with 662-nm wavelength

and 2.5-W optical power, and the light dose was

100 J/cm2, delivered at a fluency rate of 170 mW/

cm2 with a 12-mm spot size, which covered only

the detected lesion.1 The patient was kept in the

dark from the application of the photosensitizer

until she left the hospital unit, during the night.

No serious side effects or complications during or

after treatment were observed other than transient

mild local pain and moderate edema followed by a

crusted ulcer formation after 1 week.

Figure 1 shows the 10-mm tumor zone before

PDT, including the area on the left of the photo-

*CEIF, Instituto Venezolano de Investigaciones Cientıficas, Merida, Venezuela; †International Centre for TheoreticalPhysics Abdus Salam, Trieste, Italy; ‡Unidad de Cirugıa Plastica, Servicio Oncologico Hospitalario, InstitutoVenezolano de los Seguros Sociales, Caracas, Venezuela; §Facultad de Farmacia y Bioanalisis, Universidad de LosAndes, Merida, Venezuela; ¶Laboratorio de Fısica Aplicada, Universidad de Los Andes, Merida, Venezuela

© 2012 by the American Society for Dermatologic Surgery, Inc. � Published by Wiley Periodicals, Inc. �ISSN: 1076-0512 � Dermatol Surg 2012;1–3 � DOI: 10.1111/j.1524-4725.2012.02400.x

1

graph that has no visual evidence of a tumor. Fig-

ure 2 shows that, after light treatment, the crust

formed on the area of the tumor and toward a

contiguous area that was not treated with light

(Figure 3). Although we have no direct evidence,

and because this was an unexpected result, we

assumed that the left untreated side of the irradi-

ated zone was part of the BCC. Healing occurred

within 3–4 weeks, with complete regression of the

tumor confirmed by biopsy, with the observation

period of 1 year without recurrence. The aesthetic

results were acceptable (Figure 4).

Discussion

Selective accumulation of chlorine e6-PVP in tumor

cells has already been demonstrated, and this is the

basis for selective PDT and diagnosis.2 Moreover,

according to this report, the e6-PVP induced cell

death via apoptosis and also via necrosis.2 Photo-

sensitizers are known to induce cell killing through

type I reactions in which electron transfer occurs

between the light-excited photosensitizer and cellu-

lar constituents or type II reactions that involve

energy transfer between the excited photosensitizer

and molecular oxygen to produce singlet oxygen.3

For Photolon, it has been demonstrated that the

mechanism of induced cell death involves the

induction of ROS through a type I mechanism.4

The fact that, even under normal physiologic con-

ditions, ROS can oxidize blood and structural pro-

teins and inhibit the proteolytic system can explain

Figure 1. Photograph showing the 10-mm basal cell carci-noma near the nasal tip before photodynamic therapy.

Figure 2. Seven days after photodynamic therapy, photo-graph showing crusted ulcer formation in a 10-mm treatedtumor and in a contiguous untreated zone.

Figure 3. Spot laser illumination over the treated tumorarea during photodynamic therapy.

Figure 4. Eighty days after photodynamic therapy. Healingof the tumor with epithelialization and acceptable aestheticresults.

CASE REPORT OF THE EFFECT OF PHOTODYNAMIC THERAPY

DERMATOLOGIC SURGERY2

this. During oxidation, proteins can lose amino

acids or can be fragmented. Those reactions lead

to alteration of structural proteins or alteration of

enzyme functions. Overall increases in the relative

level of organic hydroxyl, carbonyl, and carboxyl-

free radical groups (alkoxyl radical RO• half-life

1 ls, peroxyl radical ROO• half-life 7 seconds, and

hydroperoxyl radical ROOH•), generating a diffus-

ible effect that can extend to nearby tissue, accom-

pany protein and amino acid oxidation. Free

radicals produced by type II reactions have a half-

life that lasts from 1 ns to 10 ls (superoxide ion

O2•� 10 ls, singlet oxygen 1O2 1 ls. and hydroxyl

radical OH• 1 ns).5 This is in agreement with the

report of deeper and more-extensive necrosis in

patients treated with Photolon than in those trea-

ted with Radachlorin and Photoditazine1 which

may be acting through a type II reaction.

The findings of this study suggest that the necrosis

and regression of the untreated tumor area shown

in Figure 2 may be related to the ROS generated at

the irradiated tumor site. It may be that the diffu-

sion of these cytotoxic agents from the irradiated

zone to the neighborhood tumor zone causes the

simultaneous development of the necrosis also on

this untreated zone. This is in agreement with the

fact that BCC has greater microvessel density than

surrounding normal tissue.6

In summary, PDT with Photolon is an effective

method for the treatment of BCC that provides

acceptable functional and aesthetic results without

major adverse effects. We hypothesize that, in

addition to its direct effect on BCC tumor cells,

Photolon-PDT generates diffusible and relatively

stable ROS so as to produce regression of contigu-

ous untreated tumors.

References

1. Stranadko EF, Purtskhvanidze VA, Radaev AA. Photodynamic

therapy for skin cancer with chlorine derivatives under the

outpatient conditions. Proceedings of 13th EMLA Congress

2008; 59.

2. Chin WWL, Heng PWS, Thong PSP, Bhuvaneswari R, et al.

Improved formulation of photosensitizer chlorin e6

polyvinylpyrrolidone for fluorescence diagnostic imaging and

photodynamic therapy of human cancer. Eur J Pharm Biopharm

2008;69:1083–93.

3. Calzavara-Pinton PG, Venturini M, Sala R. Photodynamic

therapy: update 2006. Part 1. Photochemistry and photobiology.

J Eur Acad Dermatol Venereol 2007;21:293–302.

4. Copley L, van der Watt P, Wirtz KW, Parker MI, et al.

Photolon, a chlorin e6 derivative, triggers ROS production and

light-dependent cell death via necrosis. Int J Biochem Cell Biol

2008;40:227–35.

5. Finaud J, Lac G, Filaire E. Oxidative stress. Sports Med

2006;36:327–58.

6. Chu C-Y, Cha S-T, Lin W-C, Lu P-H, et al. Stromal-cell-derived

factor-1a (SDF-a/CXCL12)-enhanced angiogenesis of human

basal cell carcinoma cells involves ERK1/2-NF-j/interleukin-6pathway. Carcinogenesis 2009;30:205–13.

Address correspondence and reprint requests to:Humberto Cabrera, PhD, Instituto Venezolano deInvestigaciones Cientıficas, Carretera a Jajı,Km 29, Merida 5101, Venezuela, or e-mail:hcabrera@ivic.gob.ve; cabrera_25@yahoo.com

CABRERA ET AL.

2012 3