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转移性黑色素瘤患者接受抗PD-1药物治疗联合放射治疗的活性和安全性。

Activity and safety of radiotherapy with anti-PD-1 drug therapy in patients with metastatic melanoma.

作者信息

Liniker E, Menzies A M, Kong B Y, Cooper A, Ramanujam S, Lo S, Kefford R F, Fogarty G B, Guminski A, Wang T W, Carlino M S, Hong A, Long G V

机构信息

Melanoma Institute Australia, The University of Sydney , Sydney, Australia.

Melanoma Institute Australia, The University of Sydney, Sydney, Australia; Royal North Shore Hospital, Sydney, Australia; Mater Hospital, Sydney, Australia.

出版信息

Oncoimmunology. 2016 Aug 19;5(9):e1214788. doi: 10.1080/2162402X.2016.1214788. eCollection 2016.

Abstract

The anti-PD-1 antibodies nivolumab and pembrolizumab are active in metastatic melanoma; however, there is limited data on combining anti-PD-1 antibody and radiotherapy (RT). We sought to review clinical outcomes of patients receiving RT and anti-PD-1 therapy. All patients receiving anti-PD-1 antibody and RT for metastatic melanoma were identified. RT and systemic treatment, clinical outcome, and toxicity data were collected. Fifty-three patients were included; 35 patients received extracranial RT and/or intracranial stereotactic radiosurgery (SRS) and 21 received whole brain radiotherapy (WBRT) (three of whom also received SRS/extracranial RT). Patients treated with extracranial RT or SRS received treatment either sequentially (RT then anti-PD-1, = 11), concurrently ( = 16), or concurrent "salvage" treatment to lesions progressing on anti-PD-1 therapy ( = 15). There was no excessive anti-PD-1 or RT toxicity observed in patients receiving extracranial RT. Of six patients receiving SRS, one patient developed grade 3 radiation necrosis. In 21 patients receiving WBRT, one patient developed Stevens-Johnson syndrome, one patient developed acute neurocognitive decline, and one patient developed significant cerebral edema in the setting of disease. Response in irradiated extracranial/intracranial SRS lesions was 44% for sequential treatment and 64% for concurrent treatment (=0.448). Likewise there was no significant difference between sequential or concurrent treatment in lesional response of non-irradiated lesions. For progressing lesions subsequently irradiated, response rate was 45%. RT and anti-PD-1 antibodies can be safely combined, with no detectable excess toxicity in extracranial sites. WBRT and anti-PD-1 therapy is well tolerated, although there are rare toxicities and the role of either anti-PD-1 or WBRT in the etiology of these is uncertain.

摘要

抗程序性死亡蛋白1(PD-1)抗体纳武单抗和派姆单抗在转移性黑色素瘤中具有活性;然而,关于抗PD-1抗体与放疗(RT)联合应用的数据有限。我们试图回顾接受放疗和抗PD-1治疗患者的临床结局。确定了所有接受抗PD-1抗体和放疗治疗转移性黑色素瘤的患者。收集了放疗和全身治疗、临床结局及毒性数据。纳入53例患者;35例患者接受颅外放疗和/或颅内立体定向放射外科手术(SRS),21例接受全脑放疗(WBRT)(其中3例还接受了SRS/颅外放疗)。接受颅外放疗或SRS治疗的患者接受序贯治疗(放疗后抗PD-1治疗,n = 11)、同步治疗(n = 16)或对在抗PD-1治疗中进展的病灶进行同步“挽救性”治疗(n = 15)。接受颅外放疗的患者未观察到过度的抗PD-1或放疗毒性。在6例接受SRS治疗的患者中,1例发生3级放射性坏死。在21例接受WBRT治疗的患者中,1例发生史蒂文斯-约翰逊综合征,1例发生急性神经认知功能减退,1例在疾病背景下发生显著脑水肿。序贯治疗时,照射的颅外/颅内SRS病灶的缓解率为44%,同步治疗为64%(P = 0.448)。同样,在未照射病灶的病灶缓解方面,序贯或同步治疗之间也无显著差异。对于随后接受照射的进展病灶,缓解率为45%。放疗和抗PD-1抗体可以安全联合,颅外部位未发现可检测到的过度毒性。WBRT和抗PD-1治疗耐受性良好,尽管存在罕见毒性,且抗PD-1或WBRT在这些毒性病因中的作用尚不确定。

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