Definitions of hyperprogressive disease in immunotherapy using tumour growth kinetics

Definition of hyperprogressive diseaseTumour typePatients[Ref.]
A Response Evaluation Criteria in Solid Tumours progression at the first evaluation with a twofold or greater increase in TGR between the period prior to treatment and upon therapyAll histologies treated with anti-PD-1/PD-L1131[16]
A tumour growth kinetics ratio ≥2, being the ratio between the slope of tumour growth prior to treatment and after start of therapyHead and neck squamous cell carcinoma34[17]
Time-to-treatment failure of less than 2 months, >50% increase in tumour burden compared with pre-immunotherapy imaging, and more than twofold increase in progression paceStage IV cancer, different tumour types155[18]
A disease progression at the first evaluation with ΔTGR exceeding 50%, with ΔTGR being the variation per month between TGR before and during treatmentNonsmall cell lung cancer406[19]
An absolute increase of ΔTGR by 50%, with ΔTGR being the variation per month of TGR before and after initiation of therapyNonsmall cell lung cancer242[20]

TGR: tumour growth rate; PD-1: programmed cell death 1; PD-L1: ligand of programmed cell death 1.