Saiag Philippe, Molinier Rafaele, Roger Anissa, Boru Blandine, Otmezguine Yves, Otz Joelle, Valery Charles-Ambroise, Blom Astrid, Longvert Christine, Beauchet Alain, Funck-Brentano Elisa
Department of General and Oncologic Dermatology, Ambroise Paré Hospital, APHP, & EA 4340 "Biomarkers in Cancerology and Hemato-Oncology", UVSQ, Université Paris-Saclay, 92104 Boulogne-Billancourt, France.
Department of Radiology, Ambroise Paré Hospital, APHP, 92104 Boulogne-Billancourt, France.
Cancers (Basel). 2022 Aug 23;14(17):4069. doi: 10.3390/cancers14174069.
To assess the role of radiotherapy in anti-PD-1-treated melanoma patients, we studied retrospectively a cohort of 206 consecutive anti-PD-1 monotherapy-treated advanced melanoma patients (59% M1c/d, 50% ≥ 3 metastasis sites, 33% ECOG PS ≥ 1, 33% > 1st line, 32% elevated serum LDH) having widely (49%) received concurrent radiotherapy, with RECIST 1.1 evaluation of radiated and non-radiated lesions. Overall (OS) and progression-free (PFS) survivals were calculated using Kaplan−Meier. Radiotherapy was performed early (39 patients) or after 3 months (61 patients with confirmed anti-PD-1 failure). The first radiotherapy was hypofractionated extracranial radiotherapy to 1−2 targets (26 Gy-4 weekly sessions, 68 patients), intracranial radiosurgery (25 patients), or palliative. Globally, 67 (32.5% [95% CI: 26.1−38.9]) patients achieved complete response (CR), with 25 CR patients having been radiated. In patients failing anti-PD-1, PFS and OS from anti-PD-1 initiation were 16.8 [13.4−26.6] and 37.0 months [24.6−NA], respectively, in radiated patients, and 2.2 [1.5−2.6] and 4.3 months [2.6−7.1], respectively, in non-radiated patients (p < 0.001). Abscopal response was observed in 31.5% of evaluable patients who radiated late. No factors associated with response in radiated patients were found. No unusual adverse event was seen. High-dose radiotherapy may enhance CR rate above the 6−25% reported in anti-PD-1 monotherapy or ipilimumab + nivolumab combo studies in melanoma patients.
为评估放疗在接受抗PD-1治疗的黑色素瘤患者中的作用，我们回顾性研究了一组连续206例接受抗PD-1单药治疗的晚期黑色素瘤患者（59%为M1c/d，50%有≥3个转移部位，33% ECOG体能状态≥1，33%为一线以上治疗，32%血清乳酸脱氢酶升高），其中49%的患者广泛接受了同步放疗，并采用RECIST 1.1标准评估放疗和未放疗的病灶。采用Kaplan-Meier法计算总生存期（OS）和无进展生存期（PFS）。放疗在早期进行（39例患者）或在3个月后进行（61例确诊抗PD-1治疗失败的患者）。首次放疗为针对1-2个靶区的大分割颅外放疗（26 Gy，每周4次，共68例患者）、颅内放射外科手术（25例患者）或姑息性放疗。总体而言，67例（32.5% [95% CI：26.1-38.9]）患者达到完全缓解（CR），其中25例CR患者接受了放疗。在抗PD-1治疗失败的患者中，放疗患者从开始抗PD-1治疗起的PFS和OS分别为16.8 [13.4-26.6]个月和37.0个月[24.6-NA]，未放疗患者分别为2.2 [1.5-2.6]个月和4.3个月[2.6-7.1]（p < 0.001）。在晚期接受放疗的可评估患者中，31.5%观察到远隔效应。未发现与放疗患者缓解相关的因素。未观察到异常不良事件。高剂量放疗可能使CR率高于黑色素瘤患者抗PD-1单药治疗或伊匹木单抗+纳武单抗联合治疗研究中报道的6%-25%。
