Kim Stefano, Spehner Laurie, Cabel Luc, Bidard François-Clément, Borg Christophe
University of Bourgogne Franche-Comté, Inserm, EFS BFC, UMR1098, RIGHT, Interactions Greffon-Hôte-Tumeur/Ingénierie Cellulaire et Génique, 25000 Besançon, France; Department of Medical Oncology, University Hospital of Besançon, 25000 Besançon, France; Clinical Investigational Center, CIC-1431, 25000 Besançon, France; Oncology Multidisciplinary Group (GERCOR), 75011 Paris, France; French Federation of Digestive Cancerology (FFCD), 21000 Dijon, France.
University of Bourgogne Franche-Comté, Inserm, EFS BFC, UMR1098, RIGHT, Interactions Greffon-Hôte-Tumeur/Ingénierie Cellulaire et Génique, 25000 Besançon, France; Department of Medical Oncology, University Hospital of Besançon, 25000 Besançon, France.
Bull Cancer. 2021 Jan;108(1):80-89. doi: 10.1016/j.bulcan.2020.12.001. Epub 2021 Jan 8.
Despite its status as a rare disease, the incidence of the squamous cell carcinoma of the anus (SCCA) is surging, especially in its metastatic form. In addition, the prognosis of initially localized diseases has not substantially changed since the 1970s with a recurrence rate of between 25-40 % after the chemoradiotherapy. The updated data from 115 patients included in the Epitopes-HPV01 and Epitopes-HPV02 trials, confirm the modified regimen of DCF (mDCF) as the treatment of choice for patients with advanced SCCA given the rate of sustained remissions and complete molecular responses observed. The carboplatin-paclitaxel regimen may be considered as an option for patients with contraindication to cisplatin or 5-FU. In chemo-refractory patients, the efficacy of anti-PD-1/PD-L1 in monotherapy is limited and only brings benefit to 10-20 % of patients, and its use cannot be generalized in the absence of an association potentiating its effectiveness. In order to better understand the immunological parameters associated with advanced SCCA, an analysis of peripheral immune responses was carried out in the Epitopes-HPV01 and 02 trials. It demonstrated the key role of CD4 Th1 specific responses of telomerase and M-MDSC as main prognostic factors for the therapeutic efficacy of DCF. Numerous combination trials are currently underway or will soon begin in localized SCCA, as well as in the first and second-line in the advanced stage. Finally, the detection of circulating tumor DNA of HPV oncoprotein E6 and E7 (HPVtc), especially by the "digital droplet PCR" technique, is highly sensitive and specific, and can be used in daily practice.
尽管肛门鳞状细胞癌(SCCA)是一种罕见疾病,但其发病率正在飙升,尤其是转移性肛门鳞状细胞癌。此外,自20世纪70年代以来,初发局限性疾病的预后并未有实质性改变,放化疗后的复发率在25%至40%之间。Epitopes-HPV01和Epitopes-HPV02试验纳入的115例患者的最新数据证实,鉴于观察到的持续缓解率和完全分子反应率,改良的DCF(mDCF)方案是晚期SCCA患者的首选治疗方案。对于对顺铂或5-氟尿嘧啶有禁忌的患者,可考虑使用卡铂-紫杉醇方案。在化疗难治性患者中,抗PD-1/PD-L1单药治疗的疗效有限,仅使10%至20%的患者获益,在缺乏增强其疗效的联合用药情况下,其应用不能一概而论。为了更好地了解与晚期SCCA相关的免疫参数,在Epitopes-HPV01和02试验中对外周免疫反应进行了分析。结果表明,端粒酶的CD4 Th1特异性反应和M-MDSC作为DCF治疗疗效的主要预后因素发挥关键作用。目前,针对局限性SCCA以及晚期一线和二线治疗,有许多联合试验正在进行或即将开展。最后,检测人乳头瘤病毒癌蛋白E6和E7的循环肿瘤DNA(HPVtc),尤其是通过“数字液滴PCR”技术进行检测,具有高度敏感性和特异性,可用于日常临床实践。