免疫检查点阻断通过扩增效应 CD8⁺ T 细胞克隆增强淋巴细胞清除性化疗诱导的抗肿瘤免疫
Immune Checkpoint Blockade Augments Lymphodepleting Chemotherapy-Induced Antitumor Immunity by Expanding Effector CD8+ T-cell Clones.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Non-surgical therapies for localized non-melanoma skin cancer in older adults: A review.
Non-surgical therapies for localized non-melanoma skin cancer in older adults: A review.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
非黑色素瘤皮肤癌(NMSC)是美国最常见的恶性肿瘤,其发病率迅速上升,且对老年人的影响尤为显著。虽然手术仍是NMSC的金标准治疗,但一个常被忽视的现实是,许多受影响的老年患者同时面临合并症、认知障碍、功能受限和就医障碍等多重问题,使手术治疗不切实际或难以实现。
因此,本综述探讨了非手术治疗(NST)作为老年患者重要替代方案的作用,重点阐述其机制、临床实用性以及针对老年人群的特殊考量。
具体而言,局部外用药物如5-氟尿嘧啶、咪喹莫特、替巴尼布林、维A酸类和三氯乙酸为浅表性病变提供了有效、创伤较小的选择,但其疗效在很大程度上依赖患者的依从性,而认知障碍或功能受限的个体可能难以保证依从性。另一方面,病灶内治疗(包括5-氟尿嘧啶和甲氨蝶呤)可提供较高的清除率且全身毒性极小,同时减少了患者自身的操作负担和每日用药需求。冷冻手术和电干燥刮除术等机械性技术提供了高效、经济的治疗手段,但需要伤口护理,部分老年患者可能难以完成。光动力疗法和放射治疗方式(SRT、IGSRT、近距离放疗和EBRT)显示出较强的短期疗效,但可能受到治疗相关不适或需要多次就诊的限制,对存在交通障碍的患者构成挑战。
重要的是,诸如hedgehog通路抑制剂和PD-1抑制剂等全身治疗对晚期或不可手术的疾病有效,但具有显著的毒性和治疗负担,限制了其对老年患者的适用性,尤其是那些存在多重用药问题的患者。
此外,本综述强调,在所有治疗模式中,NST的选择必须优先考虑老年医学原则,在疗效与安全性、舒适度、功能状态、认知能力、支持系统和患者偏好之间取得平衡。随着人口老龄化加剧以及NMSC数量同步增长,个体化、以患者为中心的诊疗以及扩大针对老年人的研究对于优化老年患者的治疗结局至关重要。
Non-melanoma skin cancers (NMSCs) represent the most common malignancies in the United States, with a rapidly rising incidence that disproportionately affects older adults. While surgery remains the gold-standard treatment for NMSCs, an often-overlooked reality is that many affected older adults face a combination of comorbidities, cognitive impairment, functional limitations, and logistical barriers that make surgical treatment impractical or unrealistic. Accordingly, this review examines the role of non-surgical therapies (NSTs) as essential alternatives for older patients, highlighting their mechanisms, clinical utility, and older adult-specific considerations. Specifically, topical agents such as 5-fluorouracil, imiquimod, tirbanibulin, retinoids, and trichloroacetic acid offer effective, less-invasive options for superficial lesions but rely heavily on adherence, which may be compromised in cognitively impaired or functionally-limited individuals.
Intralesional therapies (including 5-fluorouracil and methotrexate), on the other hand, provide high clearance rates with minimal systemic toxicity, while also reducing patient responsibility and daily application. Mechanical techniques like cryosurgery and electrodessication and curettage offer efficient, cost-effective treatments but require wound care that may be difficult for some older adults to manage.
Photodynamic therapy and radiation modalities (SRT, IGSRT, brachytherapy, and EBRT) demonstrate strong short-term efficacy but may be limited by treatment-related discomfort of the need for multiple visits, posing challenges for those with transportation barriers.
Importantly, systemic therapies such as hedgehog pathway inhibitors and PD-1 inhibitors are effective for advanced or inoperable disease, but carry significant toxicities and treatment burdens that limit their suitability for older patients, especially those with polypharmacy concerns.
Furthermore, this review emphasizes that across all modalities, NST selection must prioritize geriatric principles, balancing efficacy with safety, comfort, functional status, cognitive capacity, support systems, and patient preferences. As the aging population grows and NMSC numbers expand in parallel, individualized, patient-centered care and expanded older adult-focused research are essential to optimizing treatment outcomes for older adults.
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