Photodiagnosis and Photodynamic Therapy (2007) 4, 53—59
available at www.sciencedirect.com
journal homepage: www.elsevier.com/locate/pdpdt
Photodynamic therapy of port wine stains—–a report of 238 cases Zhong-Ping Qin MD ∗, Ke-Lei Li, Li Ren, Xue-Jian Liu Special Clinic for Hemangioma, Cancer Hospital of Linyi City, Shandong 276001, PR China
KEYWORDS Copper vapour laser; Photocarcinorin; Port wine stains; PWS; Photodynamic therapy; PDT
Summary Objective: Retrospective analysis of clinical effects of vascular acting photodynamic therapy (PDT) for the treatment of port wine stains (PWS). Methods: Between September 1997 and June 2003, a total of 238 PWS cases (2—56 years old) were treated with Photocarcinorin-mediated PDT using a copper vapour laser. Among them, 20 cases were pink lesions (Type I), 44 cases red lesions (Type II), 99 cases dark red lesions (Type III), 51 cases purple lesions (Type IV), and 24 cases nodular or thickened lesions (Type V), respectively. Patient received a slow intravenous injection of Photocarcinorin (4—5 mg/kg b.w.) and light was delivered during the drug injection at dose levels of 160—260 J/cm2 at fluence rates of 70—100 mW/cm2 . The same procedure was repeated 2—4 times for some patients. All patients were followed up for 6 months to 4 years. Results: Sixty-eight cases (28.6%) showed excellent response, 76 cases (31.9%) good response, 87 cases (36.6%) fair response and 7 cases (2.9%) poor or no response. Secondary scar formation was reported in three cases. Highest good to excellent response rates were seen in patients of 5—20 years old. PDT-induced transitional hyperpigmentation was reported in some patients but disappeared without the need of treatment within 3—6 months. Conclusion: Copper vapour laser PDT can selectively destroy PWS vessels without damage to the normal skin. If the technique is applied properly, it can cure superficial lesions and greatly improve thick lesions. © 2007 Elsevier B.V. All rights reserved.
Introduction Nevus flammeus, or port wine stains (PWS), are congenital vascular and pigmented lesions affecting 0.3% of births [1]. In China, PWS are commonly known as ‘‘red birthmarks’’ (translated from Chinese Pinyin: Hong-Tai-Ji). PWS often occur in the face, neck and scalp at birth and lesions tend
∗
Corresponding author. Fax: +86 539 8314068. E-mail address: [email protected] (Z.-P. Qin).
to become thicker and darker with time. Therefore, PWS may have profound cosmetic effects and cause great emotional depression, particularly in young male and female populations [2]. Conventional treatments used by Chinese physicians include cryotherapy, radioactive isotope patch, laser, sclerotherapy and chemical peels. Surgery and tattooing are rarely used in China. However, none of these therapies are ideal for the management of PWS. Chinese physicians started to explore the feasibility of photodynamic therapy (PDT) for treating PWS since the early 1990s. A great amount of data suggest that vascular targeting PDT can
1572-1000/$ — see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.pdpdt.2007.01.001
54
Z.-P. Qin et al.
eliminate abnormal blood vessels of PWS and might provide an effective alternative modality for treating PWS of various severities [3]. Between September 1997 and June 2003, our clinic treated 238 PWS patients using domestic photosensitizer and copper vapour laser. Results were satisfactory. This manuscript will retrospectively report clinical results of our pilot study.
Materials and methods
Table 2 Age
30 Total
Age and lesion type distribution No. of cases
Lesion type I
II
III
IV
V
16 54 84 52 32
5 11 4 0 0
7 14 21 2 0
4 27 45 22 1
0 2 14 21 14
0 0 0 7 17
238
20
44
99
51
24
Patient information Over a 6-year period (1997—2003) 238 patients with PWS (104 male and 134 female, 2—56 years old) underwent PDT treatment in our hospital, regardless of age, lesional colour, site, or extent. Among them, 175 patients (73.5%) had single lesion (i.e. diameter 9 cm or in more than one anatomic planes). The largest lesion covered almost half of the face and neck. Approximately 16% of patients had previously received radiation, cryotherapy or drug treatment and treated sites showed various degrees of scaring and abnormal pigmentation. In most cases, those treatment-induced lesions often co-existed with original PWS lesions. Patient and lesion information are summarized in Table 1. Classification of congenital vascular birthmarks has historically been confusing. In this study, PWS lesions were classified into five groups based on Waner and Suen’s method [4]: Type I — pink, flat; Type II — light red, flat; Type III — dark red, flat; Type IV — purple, slightly thicker, and Type V — significantly thicker or nodular. Each group had a total of 20 (8.4%), 44 (18.5%), 99 (41.6%), 51 (21.4%) and 24 (10.1%)
Table 1
Demographic data No. of cases
Sex Female Male
134 104
Age 30
16 54 84 52 32
Lesion location Face Neck Arm or leg Signal lesion Multiple lesions Previous treatment None Radioactive isotopes (32 P, Cryosurgery Chemical peeling
184 40 14 175 63
90
Sr)
199 23 13 3
patients, respectively. Lesion’s age distribution is summarized in Table 2.
PDT procedure A domestic photosensitizer Photocarcinorin (also known as PSD-007; provided by the Second Military Medical University, Shanghai) and copper vapour laser (Model IECu-10; Beijing Kedian Microwave Electronics Co. Ltd.) were used in this study. Photocarcinorin is derived from hematoporphyrin derivatives (HpD) and consists of a mixture of following porphyrins: 3 (or 8)-(1-methoxyethyl)-8 (or 3)-(1-hydroxyethyl) deuteroporphyrin IX (MHD), 3,8di-(1-methoxyethyl)-deuteroporphyrin IX (DMD), 3 (or 8)-(1-methoxyethyl)-8 (or 3)-vinyl-deuteroporphyrin IX (MVD), 3 (or 8)-O-(acetyloxyethyl)-8 (or 3)-(1-hydroxyethyl) deuteroporphyrin IX (AHD), hydroxyethylvinyldeuteroporphyin (HVD), hematoporphyrin IX, and protoporphyrin IX [5]. It differs from Photfrin and HpD both in chemical composition and spectral properties since the majority of hematoporphyrin (Hp) have been removed in order to enhance photodynamic effect. It has been wildly used in clinical PDT for treating various cancers in China [6]. The laser has a maximal power output of 10 W and peak wavelengths of 510.6 nm (50—75%) and 578.2 nm (25—50%). Light was delivered through an optic fiber with a flat cut tip (Beijing Kedian Microwave Electronics Co. Ltd.). Patient received slow intravenous injection (∼20 min) of Photocarcinorin (4—5 mg/kg b.w.) after passing routine allergy skin test. Light was delivered at dose levels of 160—260 J/cm2 and at fluence rates of 70—100 mW/cm2 . Light irradiation was started at the onset of drug injection to maximize the vascular effect. Light irradiation lasted 40—60 min and the overlap between drug injection and light irradiation was approximately 20 min. Lower fluence rate was used for younger patients. The diameter of illumination spot was adjusted from 2 to 10 cm. The fiber tip was positioned perpendicularly to the surface of the lesion. Larger lesions were covered by several illumination spots. The area of treatment ranged from 3 to 64 cm2 . In this pilot study, 45 cases (18.9%) received one course of treatment. Other 193 cases (81.1%), including 130 cases of single lesion and 63 cases of multiple lesions, received 2—4 courses of treatment. Patients with large, multiple, thick, dark or deep lesions were the candidates of the multiple treatment. The interval between each course was 2—3 months.
PWS PDT Table 3
55 Relationship of lesion types and therapeutic effects
Lesion type
No. of cases (%) Excellent
Good
Fair
Poor
I: n = 20 II: n = 44 III: n = 99 IV: n = 51 V: n = 24
17 (85.0) 26 (59.0) 23 (23.2) 2 (3.9) 0 (0)
2 16 42 16
(10.0) (36.4) (42.4) (31.4) 0 (0)
0 (0) 1 (2.3) 34 (34.3) 31 (60.8) 21 (87.5)
1 (5.0) 1 (2.3) 0 (0) 2 (3.9) 3 (12.5)
Total: n = 238
68 (28.6)
76 (31.9)
87 (36.6)
7 (2.9)
Anesthesia and pain control Patients might feel itching at the beginning and then a burning sensation or needle pinch pain on the area of light irradiation. Those sensation changes were most severe at about 20 min after the onset of light irradiation. Adults generally could tolerate well and did not need analgesia. EMLA cream (a lidocaine/prilocaine cream), infraorbital block or regional anesthesia could be used for those could not tolerate the pain. For younger patients, sedation with chloral hydrate or general anesthesia could be used. In this study, 52 patients received general anesthesia and 186 patients regional anesthesia, respectively.
Evaluation There are no standard evaluation criteria available to assess the effectiveness of PDT treatment of PWS. In this study we used the criteria suggested by Gilchrest for the assessment of clinical outcomes of laser therapy [7]. Similar criteria were often used by other physicians for PWS PDT evaluation in China [3]. Treatment outcomes were evaluated after over 6-month follow-up. Lesion sites were examined visually and
photographs were taken before and after treatment. Clinical outcomes were graded as: excellent — color was close to normal skin color and no scar formation; good — marked blanching, thicker lesion become flat, no scar formation; fair — blanching, thicker lesion become flat moderately; and poor — scaring, pigmentation and no blanching.
Results Clinical outcomes The period of follow up ranged from 6 months to 4 years (average 22 months). Treated areas were examined visually and outcomes were graded as excellent, good, fair or poor. Details of clinical outcomes of 238 patients are listed in Table 3. Excellent response was seen in 68 patients (28.6%) which included 17 cases (25%) of Type I lesion, 26 cases (38%) of Type II lesion, 23 (34%) cases of Type III lesion, and 2 (3%) cases of Type IV lesion. However, excellent or good response was not seen in Type V lesion which counted for a total of 24 (10.1%) patients in this study. Approximately 32% of patients showed a good response. Among them, the majority was Type III lesions (>55%). In our study, 21 Type V lesions (>87%)
Figure 1 Male, 6 years old. Type I lesion. Treatment: 180 J/cm2 at 80 mW/cm2 . (A) Before treatment. (B) One year after treatment. Note: The anomalous dilated vascular malformation of a small artery below the right lower eyelid received the same treatment but showed no response.
56
Z.-P. Qin et al.
Figure 2 Female, 22 years old. Type II lesion. Treatment: 260 J/cm2 at 100 mW/cm2 . (A) Before treatment. (B) One year after treatment.
Figure 3 Female, 17 years old. Type III lesion. Treatment: two courses of treatment of 260 J/cm2 at 100 mW/cm2 at 3-month interval. Top panel — before treatment. Bottom panel — 1 year after treatment.
PWS PDT
57
Figure 4 Female, 17 years old. Type IV lesion. Treatment: three courses of treatment of 220 J/cm2 at 90 mW/cm2 at 4-month intervals. (A) Before treatment. (B) Four months after the 1st treatment. (C) One and half years after the 3rd treatment. Table 4
Relationship of age and therapeutic effects
Patient age
30
No. of cases (%) Total
Excellent
Good
Fair
Poor
16 54 84 52 32
8 (50) 26 (48.1) 28 (33.3) 6 (11.5) 0 (0)
4 (25) 19 (35.2) 32 (38.1) 16 (30.8) 5 (15.6)
2 8 23 29 25
2 1 1 1 2
showed a fair response. Overall, there were seven patients including one Type I, one Type II, two Type IV and three Type V lesions, who showed poor or no response to PDT treatment. Among them three developed secondary scars although their PWS lesions showed good to excellent response. Other patients either had massive facial lesion involving upper lip or lesion in arm or leg. Even multiple course of treatment (>3) did not achieve satisfactory outcomes. Figs. 1—4 show the representative photographs of before and after treatment of Type I—IV lesions, respectively. Good to excellent response was seen in all age groups but younger patients (
available at www.sciencedirect.com
journal homepage: www.elsevier.com/locate/pdpdt
Photodynamic therapy of port wine stains—–a report of 238 cases Zhong-Ping Qin MD ∗, Ke-Lei Li, Li Ren, Xue-Jian Liu Special Clinic for Hemangioma, Cancer Hospital of Linyi City, Shandong 276001, PR China
KEYWORDS Copper vapour laser; Photocarcinorin; Port wine stains; PWS; Photodynamic therapy; PDT
Summary Objective: Retrospective analysis of clinical effects of vascular acting photodynamic therapy (PDT) for the treatment of port wine stains (PWS). Methods: Between September 1997 and June 2003, a total of 238 PWS cases (2—56 years old) were treated with Photocarcinorin-mediated PDT using a copper vapour laser. Among them, 20 cases were pink lesions (Type I), 44 cases red lesions (Type II), 99 cases dark red lesions (Type III), 51 cases purple lesions (Type IV), and 24 cases nodular or thickened lesions (Type V), respectively. Patient received a slow intravenous injection of Photocarcinorin (4—5 mg/kg b.w.) and light was delivered during the drug injection at dose levels of 160—260 J/cm2 at fluence rates of 70—100 mW/cm2 . The same procedure was repeated 2—4 times for some patients. All patients were followed up for 6 months to 4 years. Results: Sixty-eight cases (28.6%) showed excellent response, 76 cases (31.9%) good response, 87 cases (36.6%) fair response and 7 cases (2.9%) poor or no response. Secondary scar formation was reported in three cases. Highest good to excellent response rates were seen in patients of 5—20 years old. PDT-induced transitional hyperpigmentation was reported in some patients but disappeared without the need of treatment within 3—6 months. Conclusion: Copper vapour laser PDT can selectively destroy PWS vessels without damage to the normal skin. If the technique is applied properly, it can cure superficial lesions and greatly improve thick lesions. © 2007 Elsevier B.V. All rights reserved.
Introduction Nevus flammeus, or port wine stains (PWS), are congenital vascular and pigmented lesions affecting 0.3% of births [1]. In China, PWS are commonly known as ‘‘red birthmarks’’ (translated from Chinese Pinyin: Hong-Tai-Ji). PWS often occur in the face, neck and scalp at birth and lesions tend
∗
Corresponding author. Fax: +86 539 8314068. E-mail address: [email protected] (Z.-P. Qin).
to become thicker and darker with time. Therefore, PWS may have profound cosmetic effects and cause great emotional depression, particularly in young male and female populations [2]. Conventional treatments used by Chinese physicians include cryotherapy, radioactive isotope patch, laser, sclerotherapy and chemical peels. Surgery and tattooing are rarely used in China. However, none of these therapies are ideal for the management of PWS. Chinese physicians started to explore the feasibility of photodynamic therapy (PDT) for treating PWS since the early 1990s. A great amount of data suggest that vascular targeting PDT can
1572-1000/$ — see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.pdpdt.2007.01.001
54
Z.-P. Qin et al.
eliminate abnormal blood vessels of PWS and might provide an effective alternative modality for treating PWS of various severities [3]. Between September 1997 and June 2003, our clinic treated 238 PWS patients using domestic photosensitizer and copper vapour laser. Results were satisfactory. This manuscript will retrospectively report clinical results of our pilot study.
Materials and methods
Table 2 Age
30 Total
Age and lesion type distribution No. of cases
Lesion type I
II
III
IV
V
16 54 84 52 32
5 11 4 0 0
7 14 21 2 0
4 27 45 22 1
0 2 14 21 14
0 0 0 7 17
238
20
44
99
51
24
Patient information Over a 6-year period (1997—2003) 238 patients with PWS (104 male and 134 female, 2—56 years old) underwent PDT treatment in our hospital, regardless of age, lesional colour, site, or extent. Among them, 175 patients (73.5%) had single lesion (i.e. diameter 9 cm or in more than one anatomic planes). The largest lesion covered almost half of the face and neck. Approximately 16% of patients had previously received radiation, cryotherapy or drug treatment and treated sites showed various degrees of scaring and abnormal pigmentation. In most cases, those treatment-induced lesions often co-existed with original PWS lesions. Patient and lesion information are summarized in Table 1. Classification of congenital vascular birthmarks has historically been confusing. In this study, PWS lesions were classified into five groups based on Waner and Suen’s method [4]: Type I — pink, flat; Type II — light red, flat; Type III — dark red, flat; Type IV — purple, slightly thicker, and Type V — significantly thicker or nodular. Each group had a total of 20 (8.4%), 44 (18.5%), 99 (41.6%), 51 (21.4%) and 24 (10.1%)
Table 1
Demographic data No. of cases
Sex Female Male
134 104
Age 30
16 54 84 52 32
Lesion location Face Neck Arm or leg Signal lesion Multiple lesions Previous treatment None Radioactive isotopes (32 P, Cryosurgery Chemical peeling
184 40 14 175 63
90
Sr)
199 23 13 3
patients, respectively. Lesion’s age distribution is summarized in Table 2.
PDT procedure A domestic photosensitizer Photocarcinorin (also known as PSD-007; provided by the Second Military Medical University, Shanghai) and copper vapour laser (Model IECu-10; Beijing Kedian Microwave Electronics Co. Ltd.) were used in this study. Photocarcinorin is derived from hematoporphyrin derivatives (HpD) and consists of a mixture of following porphyrins: 3 (or 8)-(1-methoxyethyl)-8 (or 3)-(1-hydroxyethyl) deuteroporphyrin IX (MHD), 3,8di-(1-methoxyethyl)-deuteroporphyrin IX (DMD), 3 (or 8)-(1-methoxyethyl)-8 (or 3)-vinyl-deuteroporphyrin IX (MVD), 3 (or 8)-O-(acetyloxyethyl)-8 (or 3)-(1-hydroxyethyl) deuteroporphyrin IX (AHD), hydroxyethylvinyldeuteroporphyin (HVD), hematoporphyrin IX, and protoporphyrin IX [5]. It differs from Photfrin and HpD both in chemical composition and spectral properties since the majority of hematoporphyrin (Hp) have been removed in order to enhance photodynamic effect. It has been wildly used in clinical PDT for treating various cancers in China [6]. The laser has a maximal power output of 10 W and peak wavelengths of 510.6 nm (50—75%) and 578.2 nm (25—50%). Light was delivered through an optic fiber with a flat cut tip (Beijing Kedian Microwave Electronics Co. Ltd.). Patient received slow intravenous injection (∼20 min) of Photocarcinorin (4—5 mg/kg b.w.) after passing routine allergy skin test. Light was delivered at dose levels of 160—260 J/cm2 and at fluence rates of 70—100 mW/cm2 . Light irradiation was started at the onset of drug injection to maximize the vascular effect. Light irradiation lasted 40—60 min and the overlap between drug injection and light irradiation was approximately 20 min. Lower fluence rate was used for younger patients. The diameter of illumination spot was adjusted from 2 to 10 cm. The fiber tip was positioned perpendicularly to the surface of the lesion. Larger lesions were covered by several illumination spots. The area of treatment ranged from 3 to 64 cm2 . In this pilot study, 45 cases (18.9%) received one course of treatment. Other 193 cases (81.1%), including 130 cases of single lesion and 63 cases of multiple lesions, received 2—4 courses of treatment. Patients with large, multiple, thick, dark or deep lesions were the candidates of the multiple treatment. The interval between each course was 2—3 months.
PWS PDT Table 3
55 Relationship of lesion types and therapeutic effects
Lesion type
No. of cases (%) Excellent
Good
Fair
Poor
I: n = 20 II: n = 44 III: n = 99 IV: n = 51 V: n = 24
17 (85.0) 26 (59.0) 23 (23.2) 2 (3.9) 0 (0)
2 16 42 16
(10.0) (36.4) (42.4) (31.4) 0 (0)
0 (0) 1 (2.3) 34 (34.3) 31 (60.8) 21 (87.5)
1 (5.0) 1 (2.3) 0 (0) 2 (3.9) 3 (12.5)
Total: n = 238
68 (28.6)
76 (31.9)
87 (36.6)
7 (2.9)
Anesthesia and pain control Patients might feel itching at the beginning and then a burning sensation or needle pinch pain on the area of light irradiation. Those sensation changes were most severe at about 20 min after the onset of light irradiation. Adults generally could tolerate well and did not need analgesia. EMLA cream (a lidocaine/prilocaine cream), infraorbital block or regional anesthesia could be used for those could not tolerate the pain. For younger patients, sedation with chloral hydrate or general anesthesia could be used. In this study, 52 patients received general anesthesia and 186 patients regional anesthesia, respectively.
Evaluation There are no standard evaluation criteria available to assess the effectiveness of PDT treatment of PWS. In this study we used the criteria suggested by Gilchrest for the assessment of clinical outcomes of laser therapy [7]. Similar criteria were often used by other physicians for PWS PDT evaluation in China [3]. Treatment outcomes were evaluated after over 6-month follow-up. Lesion sites were examined visually and
photographs were taken before and after treatment. Clinical outcomes were graded as: excellent — color was close to normal skin color and no scar formation; good — marked blanching, thicker lesion become flat, no scar formation; fair — blanching, thicker lesion become flat moderately; and poor — scaring, pigmentation and no blanching.
Results Clinical outcomes The period of follow up ranged from 6 months to 4 years (average 22 months). Treated areas were examined visually and outcomes were graded as excellent, good, fair or poor. Details of clinical outcomes of 238 patients are listed in Table 3. Excellent response was seen in 68 patients (28.6%) which included 17 cases (25%) of Type I lesion, 26 cases (38%) of Type II lesion, 23 (34%) cases of Type III lesion, and 2 (3%) cases of Type IV lesion. However, excellent or good response was not seen in Type V lesion which counted for a total of 24 (10.1%) patients in this study. Approximately 32% of patients showed a good response. Among them, the majority was Type III lesions (>55%). In our study, 21 Type V lesions (>87%)
Figure 1 Male, 6 years old. Type I lesion. Treatment: 180 J/cm2 at 80 mW/cm2 . (A) Before treatment. (B) One year after treatment. Note: The anomalous dilated vascular malformation of a small artery below the right lower eyelid received the same treatment but showed no response.
56
Z.-P. Qin et al.
Figure 2 Female, 22 years old. Type II lesion. Treatment: 260 J/cm2 at 100 mW/cm2 . (A) Before treatment. (B) One year after treatment.
Figure 3 Female, 17 years old. Type III lesion. Treatment: two courses of treatment of 260 J/cm2 at 100 mW/cm2 at 3-month interval. Top panel — before treatment. Bottom panel — 1 year after treatment.
PWS PDT
57
Figure 4 Female, 17 years old. Type IV lesion. Treatment: three courses of treatment of 220 J/cm2 at 90 mW/cm2 at 4-month intervals. (A) Before treatment. (B) Four months after the 1st treatment. (C) One and half years after the 3rd treatment. Table 4
Relationship of age and therapeutic effects
Patient age
30
No. of cases (%) Total
Excellent
Good
Fair
Poor
16 54 84 52 32
8 (50) 26 (48.1) 28 (33.3) 6 (11.5) 0 (0)
4 (25) 19 (35.2) 32 (38.1) 16 (30.8) 5 (15.6)
2 8 23 29 25
2 1 1 1 2
showed a fair response. Overall, there were seven patients including one Type I, one Type II, two Type IV and three Type V lesions, who showed poor or no response to PDT treatment. Among them three developed secondary scars although their PWS lesions showed good to excellent response. Other patients either had massive facial lesion involving upper lip or lesion in arm or leg. Even multiple course of treatment (>3) did not achieve satisfactory outcomes. Figs. 1—4 show the representative photographs of before and after treatment of Type I—IV lesions, respectively. Good to excellent response was seen in all age groups but younger patients (
