5-氨基酮戊酸光动力治疗Olsen 3级日光性角化病的疗效评估及影响因素分析

doi:10.19401/j.cnki.1007-3639.2024.12.005

摘要/Abstract

摘要：

背景与目的：日光性角化病（actinic keratosis，AK）是具有皮肤鳞状细胞癌发展潜力的癌前病变，5-氨基酮戊酸光动力疗法（5-aminolevulinic acid photodynamic therapy，ALA-PDT）因其清除率高和美容无创的优势，已成为治疗AK的新选择，但其对以角化过度为特征的Olsen 3级AK病变的疗效仍存在争议。本研究旨在探讨ALA-PDT治疗Olsen 3级AK的疗效、安全性及影响疗效的因素。方法：对2020年1月—2023年7月在复旦大学附属华山医院皮肤科就诊的Olsen 3级AK患者进行连续4次ALA-PDT治疗，并随访至治疗后1年（伦理审批号：2019-491）。所有患者符合入组标准及排除标准。通过治疗后3个月的初始完全清除（initial complete clearance，ICC）和治疗后12个月的持续完全清除（sustained complete clearance，SCC）来评估疗效。同时收集患者治疗前的临床及病理学特征，采用单因素和多因素逻辑回归分析探讨Olsen 3级AK患者ALA-PDT治疗失败的危险因素，通过亚组分析进一步探索导致治疗抵抗和复发的危险因素。本临床试验在中国临床试验注册中心注册（注册号：ChiCTR1800019213）。本研究严格遵循《加强流行病学中观察性研究报告质量》（Strengthening the Reporting of Observational Studies in Epidemiology，STROBE）指南中的各项条目。结果：共有38例患者纳入本项研究，其中病例组8例，对照组29例，1例患者在治疗后6个月失访。治疗后3个月，86.84%的患者达到ICC（33/38），随访至12个月，87.88%达到ICC的患者维持SCC（29/33），治疗及随访期间无严重不良反应发生。多因素逻辑回归分析表明，病灶位于多个解剖亚单位是ALA-PDT治疗失败的独立危险因素（P=0.02，OR=28.43），亚组分析证实该因素与治疗抵抗相关（P=0.03，OR=97.54）。结论：ALA-PDT对Olsen 3级AK患者疗效良好且安全性高，为该类患者提供了一种无创的治疗选择。然而，病灶位于多个解剖亚单位的患者更容易出现治疗失败，提示对此类患者的治疗应提高警惕。

关键词: 日光性角化病, Olsen分级, 5-氨基酮戊酸, 光动力疗法, 治疗抵抗, 复发

Abstract:

Background and purpose: Actinic keratosis (AK) is a precancerous condition with the potential to develop into cutaneous squamous cell carcinoma. 5-Aminolevulinic acid photodynamic therapy (ALA-PDT) has emerged as a new treatment option for AK due to its high clearance rates and non-invasive cosmetic advantages. However, its efficacy in treating Olsen grade 3 AK, characterized by hyperkeratosis, remains controversial. This study aimed to investigate the efficacy and safety of ALA-PDT in treating Olsen grade 3 AK and to identify factors influencing treatment outcomes. Methods: A total of 38 patients with Olsen grade 3 AK who visited the Department of Dermatology, Huashan Hospital, Fudan University, between January 2020 and July 2023 underwent four consecutive sessions of ALA-PDT and were followed up for one year post-treatment (ethics number: 2019-491). All patients met the inclusion and exclusion criteria. Treatment efficacy was assessed by the initial complete clearance (ICC) at 3 months and the sustained complete clearance (SCC) at 12 months after treatment. Baseline clinical and pathological characteristics were collected. Univariate and multivariate logistic regression analyses were performed to explore risk factors for treatment failure in Olsen grade 3 AK patients receiving ALA-PDT. Subgroup analyses were conducted to further investigate risk factors associated with treatment resistance and recurrence. This study was registered on Chinese Clinical Trial Registry (chiCTR1800019213). The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist was followed for this study. Results: A total of 38 patients were included in this study, including 8 in the case group and 29 in the control group. One patient was lost to follow-up 6 months after treatment. At 3 months post-treatment, 86.84% of patients achieved ICC (33/38). At the 12-month follow-up, 87.88% of the patients who achieved ICC maintained SCC (29/33). No serious adverse reactions were reported during treatment and follow-up. Multivariate logistic regression analysis indicated that lesions located in multiple anatomical subunits was an independent risk factor for treatment failure (P=0.02, OR=28.43). Subgroup analysis confirmed that this factor was independently associated with treatment resistance (P=0.03, OR=97.54). Conclusion: ALA-PDT is effective and safe for treating Olsen grade 3 AK, offering a non-invasive treatment option for these patients. However, patients with lesions located in multiple anatomical subunits are more prone to treatment failure, warranting increased clinical attention in this population.

Key words: Actinic keratosis, Olsen grade, 5-aminolevulinic acid, Photodynamic therapy, Treatment resistance, Recurrence

朱沁媛, 马文涓, 栾菁, 吴文育, 陈淑君. 5-氨基酮戊酸光动力治疗Olsen 3级日光性角化病的疗效评估及影响因素分析[J]. 中国癌症杂志, 2024, 34(12): 1108-1114.

ZHU Qinyuan, MA Wenjuan, LUAN Jing, WU Wenyu, CHEN Shujun. Efficacy evaluation and influencing factor analysis of 5-aminolevulinic acid photodynamic therapy for Olsen grade 3 actinic keratosis[J]. China Oncology, 2024, 34(12): 1108-1114.

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Item	Olsen grade 3 AK			P^c value
Item	Entire cohort (n=38)	Case (n=8) ^a	Control (n=29) ^b	P^c value
Age^* (mean ± SD)/year	75.84±6.84 (63-92)	74.38±4.69 (66-80)	76.69±7.01 (63-92)	0.39
Male n (%)	6 (15.79)	0 (0.00)	6 (20.69)	0.16
No. of AK lesions ⁺ (med, IQR)	1 (1-2)	3 (2-4)	1 (1-2)	0.00^#
<5	33 (86.84)	5 (62.50)	27 (93.10)	0.03^#
≥5	5 (13.16)	3 (37.50)	2 (6.90)	-
Location of AKs				0.02^#
Face^d	28 (73.68)	3 (37.50)	24 (82.76)	NS
Scalp	1 (2.63)	0 (0.00)	1 (3.45)	NS
Hand	1 (2.63)	0 (0.00)	1 (3.45)	NS
Multi-sites^e	8 (21.05)	5 (62.50)	3 (10.34)	0.00^#
NMSC history n (%)	1 (2.63)	0 (0.00)	1 (3.45)	0.59
Pathological subtypes n (%)				0.01^#
Hyperkeratotic	10 (26.32)	4 (50.00)	6 (20.69)	NS
Acantholytic	5 (13.16)	1 (12.50)	4 (13.79)	NS
Lichenoid	6 (15.79)	1 (12.50)	5 (17.24)	NS
Bowenoid	15 (39.47)	0 (0.00)	14 (48.28)	NS
Pigmented	2 (5.26)	2 (25.00)	0 (0.00)	NS
KIN^＋ n (%)				0.01^#
Ⅰ	13 (34.21)	4 (50.00)	9 (31.03)	NS
Ⅱ	8 (21.05)	4 (50.00)	4 (13.79)	NS
Ⅲ	17 (44.74)	0 (0.00)	16 (55.17)	NS

Item	Total cases (n=8)						Resistant cases at the 3rd month (n=5)						Recurrent cases at the 12th month (n=3)
	Univariate		Multivariate analysis				Univariate		Multivariate analysis				Univariate	Multivariate analysis
			P value	OR	P value		95% CI		P value	OR	P value		95% CI	P value	OR	P value	95% CI
Age	0.38	0.89	0.35	0.71-1.12	0.66	0.89	0.46	0.67-1.19	0.43	0.85	0.36	0.60-1.21
Gender	0.16	0.32	0.12	0.20-2.74	0.29	0.22	0.20	0.02-2.20	0.38	4.12	0.30	0.28-60.93
No. of AK	0.01^#	1.70	0.12	0.87-3.33	0.09	0.92	0.94	0.02-29.49	0.18	5.52	0.42	0.09-355.03
Location of AKs	0.01^#	1.17	0.12	0.96-1.44	0.02^#	1.31	0.04^#	1.01-1.69	0.33	1.07	0.69	0.78-1.47
Multi-sites^*	0.01^#	28.43	0.02^#	1.59-508.73	0.01^#	97.54	0.03^#	1.64-5787.09	0.28	2.33	0.74	0.02-351.98
Pathological subtypes	0.17	0.99	0.98	0.50-1.94	0.76	1.18	0.64	0.58-2.42	0.10	0.38	0.24	0.08-1.89
KIN	0.05	0.20	0.09	0.03-1.25	0.10	0.17	0.09	0.02-1.33	0.31	1.38	0.84	0.07-27.85