2.

Evaluation criteria for tumor response to treatment

	WHO	RECIST v1.1	IrRC	IRECIST	ImRECIST
Dimensional	Bidimensional/ unidimensional	Unidimensional	Bidimensional	Unidimensional	Unidimensional
Target lesion	NA	Up to a maximum of two lesions per organ and five lesions total	Up to maximum five lesions per organ, 10 visceral lesions and 5 cutaneous target lesions	Per RECIST v1.1	Per RECIST v1.1
Nontarget lesion	NA	Contribute to the CR, PR, SD and PD	Nontarget progression does not define PD; can only contribute to defining CR (complete disappearance required)	Contribute to the CR, PR, SD and PD	Nontarget progression does not define PD; can only contribute to define CR (complete disappearance required)
New lesion	Always represent PD	Always represent PD	Do not define progression but preclude irCR	Represent iUPD and require a next imaging assessment to confirmation	New lesions are added to the total tumor burden along with the sum of the target lesions when measurable; when not measurable, they are not factored into the PD assessment
CR	Disappearance of all known lesions, determined by two observations not less than 4 weeks apart	Disappearance of all target and nontarget lesions and normalization of tumor marker level	Complete disappearance of all lesions (whether measurable or not, and no new lesions), confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented	ICR: meet CR per RECIST v1.1 at first or at the next assessment within 4−8 weeks after iUPD	Per RECIST v1.1
PR	50% or more decrease in total tumor load of the lesions that have been measured to determine the effect of therapy by two observations not less than four weeks apart	At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Persistence of one or more nontarget lesion(s) and/or maintenance of tumor marker level above the normal limits	Decrease in tumor burden ≥ 50% relative to baseline confirmed by a consecutive assessment at least 4 weeks after first documentation	IPR: meet PR per RECIST v1.1 at first or at the next assessment within 4−8 weeks after iUPD	Per RECIST v1.1
SD	No change (NC): A 50% decrease in total tumor size cannot be established nor has a 25% increase in the size of 1 or more measu-rable lesions have been demonstrated	Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Persistence of one or more nontarget lesion(s) and/or maintenance of tumor marker level above the normal limits	Not meeting criteria for irCR or irPR, in absence of irPD	ISD: meet SD per RECIST v1.1 at first or at the next assessment within 4−8 weeks after iUPD	Per RECIST v1.1
PD	25% or more increase in the size of one or more measurable lesions or the appearance of new lesions	At least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Or unequivocal progression of existing nontarget lesions	Increase in tumor burden ≥ 25% relative to nadir (minimum recorded tumor burden) confirmed by a repeat, consecutive assessment no less than 4 weeks from the date first documented	IUPD: PD per RECIST v1.1 but has not been confirmed at the next assessment. ICPD: in the next imaging assessment, done at 4–8 weeks after iUPD, confirms additional new lesions or a further increase in new lesions, target lesions and nontarget lesions from iUPD (sum of measures increase in target lesions ≥ 5 mm, any increase for nontarget lesions)	≥ 20% increase in SLD of target lesions and new lesions compared with baseline/nadir, can be negated by subsequent non-PD assessment ≥ 4 weeks from the date first documented; allows treatment beyond PD
CR, complete response; PR, partial response; imRECIST, immune-modified RECIST; irRC, immune-related response criteria; PD, progressive disease; iUPD, unconfirmed progressive disease; iCPD, unconfirmed progressive disease; RECIST, Response Evaluation Criteria In Solid Tumors; SLD, sum of longest diameters; nadir, minimum recorded tumor burden; NA, no application