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Patterns of failure after immunotherapy with checkpoint inhibitors predict durable progression-free survival after local therapy for metastatic melanoma.
检查点抑制剂免疫治疗后的失败模式预测转移性黑色素瘤局部治疗后的持久无进展生存期。
Checkpoint blockade Checkpoint inhibitors Immunotherapy Local therapy Melanoma Metastasectomy Pattern-of-failure
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摘要

BACKGROUND:Checkpoint inhibitors (CPI) have revolutionized the treatment of metastatic melanoma, but most patients treated with CPI eventually develop progressive disease. Local therapy including surgery, ablation or stereotactic body radiotherapy (SBRT) may be useful to manage limited progression, but criteria for patient selection have not been established. Previous work has suggested progression-free survival (PFS) after local therapy is associated with patterns of immunotherapy failure, but this has not been studied in patients treated with CPI.
METHODS:We analyzed clinical data from patients with metastatic melanoma who were treated with antibodies against CTLA-4, PD-1 or PD-L1, either as single-agent or combination therapy, and identified those who had disease progression in 1 to 3 sites managed with local therapy. Patterns of CPI failure were designated by independent radiological review as growth of established metastases or appearance of new metastases. Local therapy for diagnosis, palliation or CNS metastases was excluded.
RESULTS:Four hundred twenty-eight patients with metastatic melanoma received treatment with CPI from 2007 to 2018. Seventy-seven have ongoing complete responses while 69 died within 6 months of starting CPI; of the remaining 282 patients, 52 (18%) were treated with local therapy meeting our inclusion criteria. Local therapy to achieve no evidence of disease (NED) was associated with three-year progression-free survival (PFS) of 31% and five-year disease-specific survival (DSS) of 60%. Stratified by patterns of failure, patients with progression in established tumors had three-year PFS of 70%, while those with new metastases had three-year PFS of 6% (P = 0.001). Five-year DSS after local therapy was 93% versus 31%, respectively (P = 0.046).
CONCLUSIONS:Local therapy for oligoprogression after CPI can result in durable PFS in selected patients. We observed that patterns of failure seen during or after CPI treatment are strongly associated with PFS after local therapy, and may represent a useful criterion for patient selection. This experience suggests there may be an increased role for local therapy in patients being treated with immunotherapy.

译文

背景: 检查点抑制剂 (CPI) 已经彻底改变了转移性黑色素瘤的治疗,但是大多数用 CPI 治疗的患者最终会发展成进展性疾病。局部治疗包括手术、消融或立体定向放射治疗 (SBRT) 可能有助于控制有限的进展,但患者选择标准尚未建立。先前的研究表明,局部治疗后的无进展生存期 (PFS) 与免疫治疗失败的模式相关,但这还没有在接受 CPI 治疗的患者中进行研究。
方法: 我们分析了转移性黑色素瘤患者的临床资料,这些患者接受了抗 CTLA-4 、 PD-1 或 PD-L1 的抗体治疗,无论是单药治疗还是联合治疗, 并确定了那些在 1 到 3 个局部治疗管理的部位有疾病进展的人。独立放射学检查将 CPI 失败的模式指定为已确定的转移灶的生长或新转移灶的出现。排除诊断、缓解或 CNS 转移的局部治疗。
结果: 248 例转移性黑素瘤患者接受了 CPI 2007年 2018年治疗。七十七名患者有持续的完整反应,而 69 名患者在开始 CPI 后的 6 个月内死亡; 其余 282 名患者中,52 名 (18%) 接受了符合我们纳入标准的局部治疗。无疾病证据的局部治疗 (NED) 与 31% 的三年无进展生存期 (PFS) 和 60% 的五年疾病特异性生存期 (DSS) 相关。根据失败模式分层,在已确定的肿瘤中进展的患者三年 PFS 为 70%,而那些新转移的患者三年 PFS 为 6% (p = 0.001)。局部治疗后的五年 DSS 分别为 93% 和 31% (p = 0.046)。
结论: CPI 后寡聚进展的局部治疗可导致选定患者持久的 PFS。我们观察到 CPI 治疗期间或之后出现的失败模式与局部治疗后的 PFS 密切相关,并且可能是患者选择的有用标准。这一经验表明,在接受免疫治疗的患者中,局部治疗的作用可能会增加。

progression-free survival

肾内泌尿 基础研究 医疗诊断评价
概述  :  

肿瘤是严重危害人类健康的常见疾病,肿瘤的治疗方法主要是手术治疗、化学疗法、放射疗法和靶向治疗。随着技术的发展以及基础理论的进步,肿瘤的治疗效果也在逐渐提高。对肿瘤的治疗效果评价是肿瘤临床日常工作和新药临床试验中的非常重要的方面。从重视近期疗效,逐渐过渡到更加重视远期疗效。无进展生存期是指观察受试者进入试验到肿瘤发生恶化或死亡的时间长度,受试者只要肿瘤恶化或死亡二者其一先发生,则达到研究的终点。在药物研发的临床试验中,该指标通常用来判断肿瘤的远期疗效评价,通常作为研究

Progression   英 /prə'greʃ(ə)n/   美 /prə'ɡrɛʃən/

释    义   n. 前进;连续

例    句   Furthermore, estimates of risk for progression could have been biased by patients who died before their nephropathy might have progressed. 此外,对进展的风险估计可能有偏差,因为有些病人去世时肾病可能已经进展。

 

Free   英 /friː/   美 /fri/

释    义   adj. 免费的;自由的,不受约束的;[化学] 游离的

               vt. 使自由,解放;释放

               adv. 自由地;免费

例    句   These are all free, take any (of them) you like. 所有都是免费的,你喜欢吃什么就吃什么。

 

Survival   英 /sə'vaɪv(ə)l/   美 /sɚ'vaɪvl/

释    义   n. 幸存,残存;幸存者,残存物

同根词   surviving adj. 继续存在的;未死的;依然健在的

               survivor n. 幸存者;生还者;残存物

               survivalist n. 活命主义者;成功地活下来的人

               surviving v. 生存(survive的ing形式)

               survive vi. 幸存;活下来

               survive vt. 幸存;生还;幸免于;比...活得长

例    句   We need food and water for survival . 我们为了生存需要食物和水。

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