List of the main criteria for HPD definition

HPD definitionDrugType of tumorPatients (N)HPD (%)Predictive factorsReference
PD RECIST and increase in TGR ≥ 2mAb anti PD-1/PD-L1 (phase I)Various1319%Age ≥ 65 years[6]
PD RECIST and ΔTGR > 50%mAb anti PD-1/PD-L1NSCLC40613.8%> 2 metastatic sites[9]
PD RECIST & increase in TGR ≥ 2CKI and costimulatory moleculesVarious1827%Female[8]
Increase in TGK ≥ 2mAb anti PD-1/PD-L1HNSCC3429%Tumor relapse in RT[12]
PD RECIST and 3 criteria among:
1) TTF < 2 months;
2) increase ≥ 50% in sum of target diameters;
3) ≥ 2 new lesions in already involved organs;
4) Mets in new organs;
5) PS ECOG ≥ 2
CKINSCLC15225.7%Myeloids cell density and MPO in the tumor & low PD-L1[14]
TTF < 2 months and increase in tumor burden ≥ 50% and increase in pace of growth ≥ 2CKI and costimulatory moleculesVarious1554%EGFR, MDM2/4, DNMT3A[10]
TTF < 2 months and increase ≥ 10 mm in mesurable lesions and increase ≥ 40% of tumor burden or > 20% with apperance of new lesionsCKIVarious21415%[11]
TTF < 2 months and TGK ≥ 2 and increase in tumor volume ≥ 50%CKINSCLC13513.1%NLR > 4, LDH > UNL, STK11[15]
PD RECIST and RECIST ≥ 50% and increase in TGR ≥ 2CKIVarious5 HPD patientsMDM2/4, EGFR[16]

PD: progressive disease; PS: performance status; mAb: monoclonal antibody; CKI: cyclin-dependent kinase inhibitors; HNSCC: head and neck squamous cell carcinoma; RT: radiotherapy; MPO: myeloperoxidase; MDM2/4: Mouse double minute 2/4 homolog; DNMT3A: DNA methyltransferase 3 alpha; NLR: neutrophil lymphocyte ratio; LDH: lactate dehydrogenase; UNL: upper normal limit; STK11: Serine/threonine kinase 11