Objective response rate assessment in oncology: Current situation and future expectations

Table 1 The World Health Organization, Response Evaluation Criteria in Solid Tumors version 1.0 and Response Evaluation Criteria in Solid Tumors version 1.1 criteria¹

	WHO	RECIST v1.0	RECIST v1.1
Method	Sum of products of two longest diameters in perpendicular dimensions (bidimensional; surface area)	Sum of longest diameters of target lesions (unidimensional)	Sum of longest diameters of non-nodal target lesions and short axis of nodal target lesions (unidimensional)
No. of measured lesion	All lesions	Target lesions: maximum 5 per organ, 10 in total	Target lesions: Maximum 2 per organ, 5 in total
Response
CR	Disappearance of all known disease, confirmed at 4 wk2	Disappearance of all known disease, confirmed at 4 wk	Disappearance of all known disease, confirmed at 4 wk, lymph nodes must be < 10 mm short axis
PR	≥ 50% decrease from baseline, confirmed at 4 wk	≥ 30% decrease from baseline, confirmed at 4 wk	≥ 30% decrease from baseline, confirmed at 4 wk
SD	Neither PR nor PD criteria met	Neither PR nor PD criteria met	Neither PR nor PD criteria met
PD	≥ 25% increase, no CR, PR, or SD, new lesion (s), ≥ 25% increase in 1 lesion	≥ 20% increase over smallest sum observed, no CR, PR, or SD, new lesion(s)	≥ 20% increase over smallest sum observed, no CR, PR, or SD, new lesion(s)3. The sum must also demonstrate an absolute increase of at least 5 mm

¹Modified from Choi et al[12], and extended with adding Response Evaluation Criteria in Solid Tumors version 1.1;

²Minimum interval between baseline assessment and first response evaluation;

³On detection of new lesions, fluorodeoxyglucose-positron emission tomography scan is included. CR: Complete response; PR: Partial response; SD: Stable disease; PD: Progressive disease; WHO: World Health Organization; RECIST: Response Evaluation Criteria in Solid Tumors.

Table 2 Comparison of modified Response Evaluation Criteria in Solid Tumors, European Association for the Study of the Liver and quantitative European Association for the Study of the Liver criteria for hepatocellular carcinoma[18,19,22-25]

	mRECIST (1D criteria)	EASL (2D criteria)	qEASL (3D criteria)
CR	Disappearance of any intratumoral enhancement in all target lesions	Disappearance of any intratumoral enhancement in all target lesions	Disappearance of any intratumoral enhancement in all target lesions
PR	At least 30% decrease in the sum of max. diameters of the enhanced tumor area	At least 50% decrease in the product of max. diameter and its perpendicular of the enhanced tumor area	At least 65% decrease in the enhanced tumor volume
SD	Neither PR, nor PD	Neither PR, nor PD	Neither PR, nor PD
PD	At least 20% increase in the sum of diameters of the enhanced tumor area	At least 25% increase in the product of max. diameter and its perpendicular of the enhanced tumor area	At least 73% increase in the enhanced tumor volume

EASL: European Association for the Study of the Liver; qEASL: Quantitative European Association for the Study of the Liver; HCC: Hepatocellular carcinoma; 1D: Unidimensional; 2D: Bidimensional; 3D: Tridimensional (volumetric); CR: Complete response; PR: Partial response; SD: Stable disease; PD: Progressive disease.

Table 3 Response evaluation in example 1 and example 2 of Figure 2

	RECIST	WHO
Example 1
t1 (B vs A)	PR	PR
t2 (C vs A)	PR	PR
Example 2
t1 (Y vs X)	PR	SD
t2 (Z vs X)	PR	PR

SD: Stable disease; PR: Partial response; t₁: Time point-1; t₂: Time point-2; WHO: World Health Organization; RECIST: Response Evaluation Criteria in Solid Tumors.

Table 4 Depth of response in Figure 2

Tumor	RECIST (longest diameter)	WHO (surface)	DpR
B	4 cm	PR (13.2 cm2)	No
Y	4 cm	SD (16 cm2)	No
Z	4 cm	PR (4 cm2)	Yes

DpR: Depth of response; SD: Stable disease; PR: Partial response; WHO: World Health Organization; RECIST: Response Evaluation Criteria in Solid Tumors.

Table 5 Immune response criteria[63-66]

	irRC (2D), 2009	irRECIST (1D), 2013	iRECIST (1D), 2017	imRECIST (1D), 2018
Minimum number of target lesions	10 lesions in total; 5 lesions per organ	5 lesions in total; 2 lesions per organ	5 lesions in total; 2 lesions per organ	5 lesions in total; 2 lesions per organ
New lesions	Included in the sum of the measurements	Included in the sum of the measurements	iUPD; becomes iCPD if PD eventually confirmed	Included in the sum of the measurements
CR	Disappearance of all lesions	Disappearance of all lesions	Disappearance of all lesions	Disappearance of all lesions
PR	≥ 50% decrease from baseline	≥ 30% decrease from baseline	≥ 30% decrease from baseline	≥ 30% decrease from baseline
SD	Neither CR nor PD	Neither CR nor PD	Neither CR nor PD	Neither CR nor PD
PD	≥ 25% increase in the nadir	≥ 20% increase in the nadir (minimum 5 mm)	≥ 20% increase in the nadir (minimum 5 mm)	≥ 20% increase in the nadir (minimum 5 mm)
Confirmation of PD	Yes	Yes1	Yes2	Yes3

¹At least 4 wk after, and up to 12 wk;

²At least 4 wk after, and up to 8 wk;

³4 wk after. 1D: Unidimensional; 2D: Bidimensional; CR: Complete response; PR: Partial response; SD: Stable disease; PD: Progressive disease; iUPD: Immune unconfirmed progressive disease; iCPD: Immune confirmed progressive disease; irRECIST: İmmune-related Response Evaluation Criteria in Solid Tumors; iRECIST: İmmunotherapy Response Evaluation Criteria in Solid Tumors; irRC: İmmune-specific related response criteria; imRECIST: Immune-Modified Response Evaluation Criteria In Solid Tumors.

Table 6 Comparison of fluorodeoxyglucose-positron emission tomography response criteria[78,80,81,84]

	EORTC PET, 1999	PERCIST, 2009	iPERCIST, 2019
CMR	Complete Resolution of FDG uptake1	Complete Resolution of FDG uptake	Complete Resolution of FDG uptake
PMR	15-25% decrease of SUV after one cycle or > 25% decrease after more than one treatment cycle	≥ 30% decrease in the target tumor SULpeak	≥ 30% decrease in the target tumor SULpeak
SMD	Increase of SUV by < 25% or decrease of SUV by < 15%	Neither CR, PR nor PD	Neither CR, PR nor PD
PMD	Increase of SUV by > 25% or Increase of the longest diameter by 20% or new FDG avid lesion(s)	≥ 30% increase in SULpeak or advent of new FDG avid lesions	≥ 30% increase in SULpeak or advent of new FDG avid lesions (UPMD); Need to be confirmed by a second PET at 4-8 wk later (CPMD)

¹Indistinguishable from surrounding background. CMR: Complete metabolic response; PMR: Partial metabolic response; SMD: Stable metabolic disease; PMD: Progressive metabolic disease; UPMD: Unconfirmed progressive metabolic disease; CPMD: Confirmed progressive metabolic disease; PET: Positron emission tomography; SUV: Standardized uptake value; FDG: Fluorodeoxyglucose; SUL: Standardized uptake value, normalized to the lean body mass; EORTC: European Organization for Research in the Treatment of Cancer; PERCIST: Positron emission tomography response criteria in solid tumors; iPERCIST: İmmune positron emission tomography Response Criteria.

Table 7 The 5-point scale scores and Deauville criteria in Hodgkin Lymphoma[85-88]

Score	PET/CT scan result	At iPET	At end-of-treatment
1	No uptake	CMR	CMR
2	Uptake ≤ mediastinum	CMR	CMR
3	Liver ≥ Uptake > mediastinum	Inadequate response	Good prognosis
4	Uptake moderately higher than liver	PMR	Treatment failure
5	Uptake markedly higher than liver and/or new lesions	PMR	Treatment failure
X	New areas of uptake unlikely to be related to lymphoma

iPET: Interim positron emission tomography; CMR: Complete metabolic response; PMR: Partial metabolic response.

Table 8 Summary of current objective response assessment criteria

Response assessment criteria	Year	Imaging modalities	Assessment type	Advantages	Disadvantages
WHO	1979 and 1981	CT	Anatomic, size-based	First objective measurements of images of all lesions	Time-consuming procedure; Interobserver variability
RECIST v1.0	2000	CT, MRI	Anatomic, size-based	Easier than WHO; Measurement of "Target" and "Non-target" lesions; Less measurement errors	Only anatomic assessment
RECIST v1.1	2009	CT, MRI, PET	Anatomic, size-based	Easier than RECIST v1.0 Lymph nodes incorporated	Only anatomic assessment
mRECIST	2006	CT, MRI	Anatomic, size-based	Simpler than RECIST v1.1	Only anatomic assessment, not prospectively validated
mRECIST for HCC	2010	CT, MRI	Anatomic and functional; Based on contrast enhancement	Measurement of a viable tumor. Appropriate for loco-regional therapies	Only for HCC
EASL and qEASL	2000 and 2012	CT, MRI	Anatomic and functional; Based on contrast enhancement	qEASL is better than RECIST to predict OS; Measurement of a viable tumor	Only for HCC
Choi criteria	2007	CT	Anatomic and functional; Based on tumor density	Validated for GIST, more precise than RECIST; Measurement of a viable tumor	Only for GIST
Morphologic Response	2009	CT	Anatomic and functional; Based on morphologic changes	Appropriate for bevacizumab treatment	For CRC liver met., not prospectively validated
irRC	2009	CT, MRI	Anatomic, size-based	For the treatment with immune-checkpoint inhibitors, capture of atypical response (pseudoprogression)	The variability of interpretation
irRECIST	2013	CT, MRI
iRECIST	2017	CT, MRI
imRECIST	2018	CT, MRI
EORTC PET PERCIST 1.0 iPERCIST	1999, 2009, 2019	PET	Metabolic	Detection of early metabolic changes	Limited resolution for tumors less than 0.4 cm. In NSCLC patients, retrospective
MDA criteria	2004 and 2010	CT, MRI, XR, SS	Anatomic	A comprehensive evaluation of bone metastasis	Only for bone metastasis
RANO	2010	MRI	Anatomic and functional; Based on contrast enhancement	Capture of pseudoprogression and pseudoresponse	Only for brain tumors

CT: Computerized tomography; MRI: Magnetic resonance imaging; PET: Positron emission tomography; XR: Plain radiography; SS: Skeletal scintigraphy; WHO: World Health Organization; RECIST: Response Evaluation Criteria in Solid Tumors; EORTC: European Organization for Research in the Treatment of Cancer; iPERCIST: İmmune positron emission tomography Response Criteria; NSCLC: Non-small-cell lung cancer; GIST: Gastrointestinal stromal tumors; CRC: Colorectal cancer; mRECIST: Modified Response Evaluation Criteria In Solid Tumors; irRECIST: İmmune-related Response Evaluation Criteria in Solid Tumors; iRECIST: İmmunotherapy Response Evaluation Criteria in Solid Tumors; irRC: İmmune-specific related response criteria; imRECIST: Immune-Modified Response Evaluation Criteria In Solid Tumors; EASL: European Association for the Study of the Liver; qEASL: Quantitative European Association for the Study of the Liver; MDA: MD Anderson; OS: Overall survival; HCC: Hepatocellular carcinoma.

Table 9 Radiation dose in adults for some radiology procedures[125]

Procedure	Approximate effective radiation dose	Comparable to natural background radiation for
Chest X-ray	0.1 mSv	10 d
CT-Head	2 mSv	8 mo
CT-Thorax	7 mSv	2 yr
CT–Abdomen and Pelvis	10 mSv	3 yr
PET/CT	25 mSv	8 yr

CT: Computed tomography; PET: Positron emission tomography; mSV: Millisievert.