来源：中华医学会胸心分会
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对非小细胞肺癌免疫治疗中超进展定义的说明
— 结论—
这项对NSCLC患者的回顾性队列研究结果表明，之前5种超进展（HPD）的定义与肿瘤的生物学行为无关。
我们制定一个新的标准，将ΔTGR定义为肿瘤免疫治疗前后的生长速率差异，以100为临界，ΔTGR大于100与超进展的特征符合（如肿瘤动力学的增加和更低生存率）。
需要对更大的患者群体进行额外的研究，以确认该定义的准确性和有效性。
The findings of this retrospective cohort study of patients with NSCLC suggest that the previous 5 definitions of HPD were not associated with the same tumor behavior. A new definition, based on ΔTGR of greater than 100, appeared to be associated with the characteristics expected with HPD (increase of the tumor kinetics and poor survival). Additional studies on larger groups of patients are necessary to confirm the accuracy and validate this proposed definition.
— 背景—
在一些研究中，PD-1/PD-L1抑制剂作为单一药物治疗的肺癌患者会出现超进展。然而，使用不同的HPD定义会导致对肿瘤生物学行为描述的混乱。
本研究旨在评估每一个HPD定义的准确性，以确定晚期非小细胞肺癌（NSCLC）患者HPD的发生率及与免疫检查点抑制剂（ICI）治疗不良结局的相关性，并在所有先前的HPD标准的基础上，提供一个优化的、一致性较好的定义。 Hyperprogressive disease (HPD) is an aggressive pattern of progression reported for patients treated with programmed cell death 1 (PD-1)/programmed cell death 1 ligand (PD-L1) inhibitors as a single agent in several studies. However, the use of different definitions of HPD introduces the risk of describing different tumoral behaviors.To assess the accuracy of each HPD definition to identify the frequency of HPD and the association with poorer outcomes of immune-checkpoint inhibitor (ICI) treatment in patients with advanced non-small cell lung cancer (NSCLC) and to provide an optimized and homogenized definition based on all previous criteria for identifying HPD.
— 方法—
这项回顾性队列研究包括2012年11月1日至2017年4月5日在8家法国机构接受PD-1/PD-L1抑制剂治疗的406名晚期非小细胞肺癌患者。
应用实体瘤反应评估标准（RECIST）1.1定义可测量的病灶，在ICI治疗开始前至少进行2次CT扫描，在治疗期间进行1次CT扫描。数据分析时间为2012年11月1日至2019年8月1日。
主要结果和措施：明确不同定义下HPD的发病率，每种HPD与总生存率之间的关联。在治疗前和治疗过程中计算先前定义中使用的所有动力学指标，如肿瘤生长速率（TGR）或肿瘤生长动力学（TGK）。
This retrospective cohort study included 406 patients with advanced NSCLC treated with PD-1/PD-L1 inhibitors from November 1, 2012, to April 5, 2017, in 8 French institutions. Measurable lesions were defined using the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria on at least 2 computed tomographic scans before the initiation of ICI therapy and 1 computed tomographic scan during treatment. Data were analyzed from November 1, 2012, to August 1, 2019Exposures: Advanced NSCLC and tretment with PD-1/PD-L1 inhibitors.Main outcomes and measures: Association of the definition with the related incidence and the HPD subset constitution and the association between each HPD definition and overall survival. All dynamic indexes used in the previous proposed definitions, such as the tumor growth rate (TGR) or tumor growth kinetics (TGK), were calculated before and during treatment.
— 结果—
在406例非小细胞肺癌患者中（男性259例，占63.8%；ICI治疗开始时的中位年龄64例，占30-91%），不同的定义下HPD的发生率在5.4%到18.5%。
这些不同定义之间的一致性从33.3%到69.3%不等。
对于每个定义，HPD与较低的生存率相关（中位总生存率范围，3.4至6.0[95%CI，3.7-9.4]个月）。
治疗前和治疗中TGR的差异（ΔTGR）与总体生存率差的相关性最大，并且它有最高的能力将HPD患者与未被归类为HPD的进行性疾病患者区分开来。
此外，本研究还确定了一个最佳阈值，即ΔTGR大于100。
Among the 406 patients with NSCLC included in the analysis (259 male [63.8%]; median age at start of ICI treatment, 64 [range, 30-91] years), the different definitions resulted in incidences of the HPD phenomenon varying from 5.4% (n = 22; definition based on a progression pace >2-fold and a time to treatment failure of <2 months) to 18.5% (n = 75; definition based on the TGR ratio). The concordance between these different definitions (using the Jaccard similarity index) varied from 33.3% to 69.3%. For every definition, HPD was associated with poorer survival (range of median overall survival, 3.4 [95% CI, 1.9-8.4] to 6.0 [95% CI, 3.7-9.4] months). The difference between TGR before and during therapy (ΔTGR) was the most correlated with poor overall survival with an initial plateau for a larger number of patients and a slower increase, and it had the highest ability to distinguish patients with HPD from those with progressive disease not classified as HPD. In addition, an optimal threshold of ΔTGR of greater than 100 was identified for this distinction.
来源：知识城邦作者：多喝热水
来源：CSTCVS1985 中华医学会胸心分会
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