表 1.

NSCLC患者的HPD研究

Studies of HPD in NSCLC

Author	Incident rate, NSCLC included	Treatment lines	Criteria	Clinical or biological predictors
HPD: hyperprogressive disease; NSCLC: non-small cell lung cancer; ICIs: immune checkpoint inhibitors; TTF: time to treatment failure; TGR: tumor growth rate; TGK: tumor growth kinetic; ECOG PS: Eastern Cooperative Oncology Group performance status; RECIST: Response Evaluation Criteria in Solid Tumor; PD-L1: programmed death ligand 1; PD-1: programmed cell death 1
Kato, 2017[10]	38 NSCLC/3 HPD	Anti-PD-1, anti-PD-L1, anti-CTLA4 or other investigational ICIs Different treatment lines	TTF < 2 months, > 50% increase in tumor burden compared with baseline pre-IO imaging, and > 2-fold increase in progression pace	MDM2/MDM4 alteration and EGFR mutation
Kim, 2018[12]	17% HPD (37/220 NSCLC)	ICI monotherapy，Line of therapy not clarified	TGK (without details)	None
Kim, ASCO 2019[8]	55 (21% HPD) according TGK; 54 (20% HPD) according TGR ratio; 98 (37% HPD) according to TTF < 2 months; Retrospective trial (only NSCLC included)	Anti-PD-1, anti-PD-L1, Different treatment lines	Defined by TGK≥2, TGR ratio≥2 or TTF < 2 months	Higher frequency of severely exhausted (TIGIT+PD1+) CD8 T-cells and lower frequency of circulating effector memory (CD45RA- CCR7-) CD8 T cells
Ferrara, 2018[7]	14% HPD (56/406 NSCLC treated with IO) 5% HPD (3/59 NSCLC treated with chemotherapy)	Anti-PD-1 or anti-PD-L1 as monotherapy or combination with anti-CTLA4 Different treatment lines	Disease progression at the first evaluation and > 50% change in TGR	> 2 metastatic sites before immunotherapy
Kim, 2019[5]	14.3% (48/335 NSCLC) had HPD by volumetric assessment and 13.1% (44/335) had HPD as by one-dimensional criteria	Anti-PD-1, anti-PD-L1, Different treatment lines	HPD defined according to one-dimensional or volumetric time-dependent criteria	Volumetric definition of HPD correlated with overall survival; High derived neutrophil-lymphocyte ratio correlated with HPD; 3 (18%) out of 16 HPD patients had LKB1 mutation
Matos Garcia, 2018[15]	15% (33/214) HPD (different tumor types included, NSCLC n=30)	Anti-PD-1 or anti-PD-L1 as monotherapy or combination Different treatment lines	TTF < 2 months and: (1) increase ≥20% in target tumor burden plus multiple new lesions or (2) increase of ≥40% in target tumor burden compared with baseline	None
Abbar, 2021[14]	169 ICI-treated patients included. HPD accounting for 11.3%, 5.7%, 17.0%, 9.6% and 31.7% patients, according to TGR ratio, ΔTGR, TGK, RECIST and TTF definitions	82.2% patients received nivolumab, 10.7% with Pembrolizumab and 7.1% with combination of nivolumab plus ipilimumab. 83.4% patients received the treatment as second-, or subsequent-line settings	The HP incidence rate was calculated according to five definitions (TGR ratio, ΔTGR, TGK, RECIST and TTF)	None
Lo Russo, 2019[6]	25.7% (39/152 NSCLC evaluable)	Anti-PD-1 or anti-PD-L1 as monotherapy or combo with anti-CTLA4 Different treatment lines	HPD on the basis of 3 concomitant out of the 5 possible criteria: TTF < 2 months, ECOG PS≥2 during the first 2 months, appearance of at least 2 new lesions in an organ, spread of the disease to a new organ, increase ≥50% in the sum of target lesions major diameters	Clustered macrophages with epithelioid morphology and co-localization of CD163, PD-L1, and CD33 markers (defined as complete phenotype)