Photodynamic therapy and cryotherapy for oral precancerous lesions
Date Issued
2008
Date
2008
Author(s)
Yu, Chuan-Hang
Abstract
Background: Oral leukoplakia (OL), oral erythroleukoplakia (OEL), and oral verrucous hyperplasia (OVH) are three common oral precancerous lesions. In this study, we used two conservative treatment modalities, topical 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) and cotton-swab cryotherapy (CSC), for treatment of these lesions. In addition, we also used immunohistochemistry (IHC) to study whether the expression of apoptosis-associated proteins in oral precancerous lesions before PDT could be a biomarker to predict the treatment outcomes of topical ALA-PDT.ethods: Thirty-six OVH lesions, 65 OL lesions, and 20 OEL lesions were treated with topical ALA-PDT once a week and 32 OL lesions were treated with the same topical ALA-PDT twice a week. Their clinical outcomes between 2 different groups were compared by chi-square test. We also assessed what clinicopathological parameters of OVH lesions could influence PDT treatment outcomes. Lesion response was characterized into three categories: complete response (CR), partial response (PR), and no response (NR). IHC was performed with antibodies against Bak, Mcl-1, caspase-3, caspase-8, caspase-9, p53, p21, or PCNA protein in 18 OVH and 40 OL biopsy specimens taken before PDT. Both the labeling indices (LIs) and staining intensity (SI) of cytoplasmic or nuclear staining by each antibody were recorded. The means of surface keratin thickness or labeling score (LS, defined as LI × SI) were statistically compared between the CR and PR or NR group. Sixty OL lesions from 47 patients were treated with CSC once 2 weeks until CR of the lesion. esults: All 36 OVH lesions showed CR after an average of 3.8 treatments of topical ALA-PDT. The 65 OL lesions treated with topical ALA-PDT once a week showed CR in 5, PR in 33, and NR in 27. The 32 OL lesions treated with the same topical ALA-PDT twice a week demonstrated CR in 11 and PR in 21. The 32 OL lesions treated twice a week had a significantly better clinical outcome than the 65 OL lesions treated once a week (P < 0.001). The 20 OEL lesions treated with topical ALA-PDT once a week showed CR in 17 and PR in 3. The 20 OEL lesions treated once a week had a significantly better clinical outcome than the 65 OL lesions treated once a week (P = 0.000). In addition, OVH lesions with the clinical appearance of a mass, with the greatest diameter < 1.5 cm, with the pink color, with epithelial dysplasia, or with the surface keratin layer ≦ 40 μm needed significantly less mean treatment numbers of PDT to achieve a CR than OVH lesions with the clinical appearance of a plaque or a combination type of peripheral plaque and central mass (P = 0.000), with the greatest diameter ≧ 1.5 cm (P = 0.011), with the white color (P = 0.000), without epithelial dysplasia (P = 0.043), or with the surface keratin layer > 40 μm (P = 0.003), respectively. Multivariate analysis showed that only the clinical appearance of OVH lesions was the independent factor (P = 0.0069) to predict the PDT treatment outcome. IHC results revealed that the Bak LS was significant higher in the CR group than in the PR or NR groups (P = 0.003). A significant difference in the Bak/Mcl-1 LS ratio was also found between the CR and PR or NR groups (P = 0.02). We also showed a significant difference in the surface keratin thickness between the CR and PR or NR groups (P = 0.036). All 60 OL lesions treated with CSC showed CR after an average of 6.3 treatments. OL lesions on the oral mucosal sites other than the tongue, < 2 cm2, with epithelial dysplasia, or with the surface keratin thickness < 55 μm needed significantly less treatment number of CSC to achieve a CR than OL lesions on the tongue (P = 0.003), ≧ 2 cm2 (P = 0.024), without epithelial dysplasia (P = 0.033), or with the surface keratin thickness ≧ 55 μm (P = 0.045), respectively. Multivariate analyses showed that only the location (P = 0.000176) and area (P = 0.021280) of OL lesions were independent factors to influence the treatment number of cryotherapy to achieve a CR.onclusion: Topical ALA-PDT is a very effective treatment modality for OVH lesions. For OVH lesions less than or equal to 3.1 cm in greatest diameter, CR of the lesions can be achieved by less than 7 treatments of topical ALA-PDT once a week. The PDT treatment outcome for OVH depends on the clinical appearance, size, color, epithelial dysplasia, and surface keratin thickness of the lesion. The clinical appearance of OVH lesions is the only independent factor affecting the PDT treatment outcome. OL lesions treated with topical ALA-PDT twice a week have a significantly better clinical outcome than OL lesions treated with the same PDT protocol once a week. OEL lesions treated with topical ALA-PDT once a week have a significantly better clinical outcome than OL lesions treated with the same PDT protocol once a week. The Bak LS and the Bak/Mcl-1 LS ratio in tissue sections of OVH and OL lesions before PDT can be used as biomarkers to predict the PDT treatment outcomes. CSC technique is a simple, safe, easy, and conservative treatment modality for OL lesions. For OL lesions with the surface area ranging from 0.1 to 6.5 (mean, 1.8) cm2, CR of the lesion can be achieved by less than 7 CSC treatments in average. OL lesions on oral mucosal sites other than the tongue, with dysplasia, and with thinner surface keratin layer needed significantly less treatment number of CSC to achieve a CR than OL lesions on the tongue, without dysplasia, and with thicker surface keratin layer, respectively.
Subjects
5-aminolevulinic acid
oral premalignant lesion
photodynamic therapy
immunohistochemistry
cryotherapy
SDGs
File(s)![Thumbnail Image]()
Loading...
Name
ntu-97-D94422004-1.pdf
Size
23.32 KB
Format
Adobe PDF
Checksum
(MD5):3204dce858f85439957b3718500444e7