Forth Summary for New response evaluation criteria in solid tumors: Revised RECIST guideline (version 1.1)

 

1. Evaluation of target lesions:

• Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in short axis to <10 mm.
• Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
• Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. 
• Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on the study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).[20% increase+5mm absolute increase]

2. Evaluation of non-target lesions:

• While some non-target lesions may actually be measurable, they need not be measured and instead should be assessed only qualitatively at the time points specified in the protocol.
• Complete Response (CR): Disappearance of all non-target lesions and normalisation of tumour marker level. All lymph nodes must be non-pathological in size (<10 mm short axis).
• Non-CR/Non-PD: Persistence of one or more non-target lesion(s) and/or maintenance of tumour marker level above the normal limits.
• Progressive Disease (PD): Unequivocal progression of existing non-target lesions. (Note: the appearance of one or more new lesions is also considered progression). 

3. Evaluation of best overall response: 

• The best overall response is the best response recorded from the start of the study treatment until the end of treatment taking into account any requirement for confirmation.
• The patient’s best overall response assignment will depend on the findings of both target and non-target disease and will also take into consideration the appearance of new lesions. 
• Furthermore, depending on the nature of the study and the protocol requirements, it may also require confirmatory measurement. 
• Specifically, in non-randomized trials where the response is the primary endpoint, confirmation of PR or CR is needed to deem either one the ‘best overall response’  

3.1 Time point response: 

It is assumed that at each protocol specified time point, a response assessment occurs. 

Table 1 on the next page provides a summary of the overall response status calculation at each time point for patients who have measurable disease at baseline.

Table 2 is to be used when patients have non-measurable (therefore non-target) disease only. 

 

3.2  Missing assessments and inevaluable designation  [NE ; Not NE unless.... ]

• When no imaging/measurement is done at all at a particular time point, the patient is not evaluable (NE) at that time point. 
• If only a subset of lesion measurements are made at an assessment, usually the case is also considered NE at that time point, unless a convincing argument can be made that the contribution of the individual missing lesion(s) would not change the assigned time point response. This would be most likely to happen in the case of PD. 

e.g. if a patient had a baseline sum of 50 mm with three measured lesions and at follow-up only two lesions were assessed, but those gave a sum of 80 mm, the patient will have achieved PD status, regardless of the contribution of the missing lesion. 

3.3 Best overall response: all time points

The best overall response is determined once all the data for the patient is known.

• Best response determination in trials where confirmation of complete or partial response IS NOT required: 

Best response in these trials is defined as the best response across all time points.

 (e.g , a patient who has SD at first assessment, PR at second assessment, and PD on last assessment has a best overall response of PR). 

When SD is believed to be the best response, it must also meet the protocol specified minimum time from baseline. If the minimum time is not met when SD is otherwise the best time point response, the patient’s best response depends on the subsequent assessments. 

(e.g. a patient who has SD at first assessment, PD at second and does not meet minimum duration for SD, will have the best response of PD. The same patient lost to follow-up after the first SD assessment would be considered invaluable. )

• Best response determination in trials where confirmation of complete or partial response IS required: Complete or partial responses may be claimed only if the criteria for each are met at a subsequent time point as specified in the protocol (generally 4 weeks later). the best overall response can be interpreted as in Table 3. 

 

 

Note:

a If a CR is truly met at first time point, then any disease seen at a subsequent time point, even disease meeting PR criteria relative to baseline, makes the disease PD at that point (since disease must have reappeared after CR). 

Best response would depend on whether minimum duration for SD was met. 

However, sometimes ‘CR’ may be claimed when subsequent scans suggest small lesions were likely still present and in fact the patient had PR, not CR at the first time point. Under these circumstances, the original CR should be changed to PR and the best response is PR 

Q: What is "confirmation of response "? When ?

• In non-randomised trials where response is the primary endpoint, confirmation of PR and CR is required to ensure responses identified are not the result of measurement error.
• in randomised trials (phase II or III) or studies where stable disease or progression are the primary endpoints, confirmation of response is not required since it will not add value to the interpretation of trial results. 
• However, elimination of the requirement for response confirmation may increase the importance of a central review to protect against bias, in particular in studies which are not blinded.