RECIST 1.1

The guidelines

The revised RECIST guidelines (version 1.1) are available here for free with permission from the European Journal of Cancer (EJC). The guidelines and accompanying articles were published in a special issue of EJC in January 2009.

pictopdf_16x16_2017 guidelines


Questions and clarifications

If your question is not addressed below, please contact us.

Target lesions

The definition of SD: a clarification

In the main article on page 233 the definition of SD is written as “Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.”

It should be read as: “Neither sufficient shrinkage (compared to baseline) to qualify for PR nor sufficient increase (taking as reference the smallest sum diameters while on study) to qualify for PD.

A confirmed PR at a next visit is considered to be a continuing PR unless the criteria for PD are met – the subsequent response is not based on the change from baseline but the change from the nadir.

For instance if the sum of longest diameters is 165 mm at baseline, 63 mm at week 8 and 65 mm at week 16, the target lesion response at week 16 is continued partial response.

However, for non-randomised studies, PRs must be confirmed after 4 weeks.  In this example, if the study is randomized and PR was confirmed at 12 weeks, the response at 16 weeks would be ongoing PR.  In the case of a non-randomized trial, if the criteria for PR are only just met at the first assessment, and are clearly not met on the confirmatory scan, it is suggested that the imaging be carefully reviewed to clarify the best response. This is an ongoing PR as the criteria for progression have not been met.

“Paired” organs

Questions often arise concerning the rule of selecting maximum 2 target lesions per organ, when it comes to paired organs (i.e. lung, kidney, ovaries, lymph nodes). In our analyses, ‘lung’, ‘kidney’, ‘ovaries’, ‘lymph nodes’ etc are considered as 1 organ, irrespective of the number of parts they may be made up of.

Of note, if there are multiple nodal chains/regions, consider selecting one from each, with a maximum of two for this organ. Other nodal lesions can be followed as non-target.

Coalesced lesions

When lesions coalesce, forming a conglomerate, a plane between them may be maintained that would aid in obtaining maximal diameter measurements of each individual lesion. If the lesions have truly coalesced such that they are no longer separable, the vector of the longest diameter in this instance should be the maximal longest diameter for the coalesced lesion. In case of nodal lesions, the short axis of the coalesced lesion should be taken into account.

Similarly, if a target and non-target lesion coalesce, there is usually a plane of separation between the lesions which should make measuring the target lesion component possible. If it is not, then the longest diameter in this instance should be the maximal longest diameter for the coalesced lesion.

In general coalesced lesions are indicative of worsening disease and the possibility of disease progression.

Non-Target lesions

Text in relation to content table 1

According to the article, a reappearing lesion is not PD if the prior patient ‘status’ was PR or SD. Does ‘prior patient status’ refer to the target lesion assessment or the overall response. Prior status refers to the overall response, not each lesion alone.

In case there is only 1 target lesion, with no non-target lesions, if the target lesion disappears and then re-appears, this would be considered to be PD, providing that if the lesion is a node, it was ≥ 10 mm (i.e malignant).  However, a single target lesion that disappears and reappears, in the presence of stable non target lesions, would not be considered PD.

New lesions

Should new lesions be followed-up as target/non-target?

Progressive Disease (PD) is defined as 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 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).

In most trial protocols, after the observation of PD, by for instance the development of a new lesion, tumor measurements would no longer necessarily be recorded. It is possible that a new lesion is questionable and a decision is made to reevaluate at the next assessment.  Other than that, it is not clear what the purpose of designating a new lesion as target or non-target would be, since a new lesion that is certain, indicated a PD status.

Does a new lesion always result in PD?

Lesions that disappear and reappear do not automatically result in PD unless

  • Other criteria are also met (new lesions, increase in the sum of longest diameters ≥ 20%) OR
  • CR (overall) was definitively (*) assigned at the previous assessment. In this scenario, the reappearance of any malignant lesion results in PD.

(*) It is recommended that CR in previous cycle is confirmed – lesions may have in fact always been present but have been indistinct.  In such cases, PR may be appropriate for both assessments

New lymph node lesions

Nodes that have a short axis < 10 mm are considered non-pathological and should not be recorded, they are considered pathological only if they are larger than 15mm. Therefore, if the node is bigger than 15 mm, it is a new lesion and PD.

Nodes that have a short axis≥ 10 to <15 mm are considered non-targeted lesions and should be followed. So if in a subsequent assessment, the node is bigger than 15 mm, it is a non-target lesion PD.

Lymph nodes

Abnormal lymph node

If an abnormal lymph node (recorded as Target or Non Target) ‘disappears’ (i.e cannot be seen for Non Target nodes or is < 10 mm) but then ‘reappears’ (i.e. visible for Non Target nodes or ≥ 10mm for nodes considered Target lesions at baseline)  is this considered to be continued CR or PD?

Nodes require special consideration as nodes <10 mm are considered benign.  Thus, a node is only considered to have ‘reappeared’ if it is ≥ 10 mm (Target lesion) or has unequivocally progressed (Non Target lesion).

As always, the overall context must be considered. Patients with bulky non nodal disease in CR (*), in whom a single node becomes visible on a CT scan, with no evidence of recurrence elsewhere, should ideally be reimaged prior to a decision regarding recurrence being made.

(*) It is recommended that CR in previous cycle is confirmed – lesions may have in fact always been present but have been indistinct.  In such cases, PR may be appropriate for both assessments

Two target lesions per organ, applied to lymph nodes

Nodes are considered to be one organ. Therefore, at most 2 target nodal-lesions can be selected. If there are multiple chains/regions, consider selecting one from each, with a maximum of two for this organ. Other nodal lesions can be followed as non-target. For hematologic malignancies, modified criteria can be considered in the protocol.

Double the slice thickness/interval & lymph nodes

It is strongly recommended that slice thickness of 5 mm should be used.

Coalesced nodal lesions

When nodal lesions coalesce, forming a conglomerate, a plane between them may be maintained that would aid in obtaining maximal diameter measurements of each individual lesion. If the lesions have truly coalesced such that they are no longer separable, the short axis of the coalesced lesion should be taken into account.

FDG-PET

FDG-PET correlation with CT

The section on FDG-PET mentions that correlation with CT is warranted for new lesions, and that PD should be declared if the hot spot on PET corresponds to a progressing lesion on CT.

If the hot spot on PET corresponds to a target lesion that has enlarged, but the sum of the target measurements does not show an increase that is sufficient for PD (other target lesions have not enlarged or have actually decreased), the FDG-PET does not override the assessment following the measurement rules of RECIST 1.1. FDG-PET in RECIST 1.1 is considered to complementary.

Similarly, if there is a hot spot on FDG-PET (baseline PET was not available) that is not associated with a new CT (or MRI) lesion, the response should be assigned based on the results of the CT (MRI) imaging.

Other

Surgery/radiotherapy and RECIST

For most studies using RECIST, surgery or radiotherapy prior to progression would be a major protocol deviation. If this is foreseen as a study procedure (i.e., you know this will happen and are allowing it) then the protocol should explicitly state how this will be handled for the interpretation of response.

In principle, these lesions will no longer be part of the assessment. This creates the situation of missing assessments: 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, then usually this 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.

Tumor assessment interval

Frequency of tumour re-evaluation while on treatment should be protocol specific and adapted to the type and schedule of treatment. However, in the context of phase II studies where the beneficial effect of therapy is not known, follow-up every 6–8 weeks (timed to coincide with the end of a cycle) is reasonable. Smaller or greater time intervals than these could be justified in specific regimens or circumstances. The protocol should specify which organ sites are to be evaluated at baseline (usually those most likely to be involved with metastatic disease for the tumour type under study) and how often evaluations are repeated (see EJC 45(2009)228-247, p236).

RECIST calculator

The RECIST committee does not provide a tool for calculating the response categories. Some companies offer calculators. However, it is easy to set up an excel spreadsheet to do these calculations.

 


Tools

Below are examples of case report forms that can be used to collect information to measure response according to RECIST 1.1

pictopdf_16x16_2017 Initial measurement form
pictopdf_16x16_2017 Follow-up measurement form


Archived news

Hear Lesley Seymour and Jan Bogaerts discuss with Helen Saul of EJC News the challenges and possibilities for RECIST.

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