RECIST Guidelines

EUROPEAN JOURNAL OF CANCER
4 5 ( 2 0 0 9 ) 2 2 8 2 4 7
available at www.sciencedirect.com
journal homepage: www.ejconline.com
New response evaluation criteria in solid tumours:

Revised RECIST guideline (version 1.1)
E.A. Eisenhauera,*, P. Therasseb, J. Bogaertsc, L.H. Schwartzd, D. Sargente, R. Fordf,
J. Danceyg, S. Arbuckh, S. Gwytheri, M. Mooneyg, L. Rubinsteing, L. Shankarg, L. Doddg,
R. Kaplanj, D. Lacombec, J. Verweijk
a
National Cancer Institute of Canada Clinical Trials Group, 10 Stuart Street, Queens University, Kingston, ON, Canada
GlaxoSmithKline Biologicals, Rixensart, Belgium
c
European Organisation for Research and Treatment of Cancer, Data Centre, Brussels, Belgium
d
Memorial Sloan Kettering Cancer Center, New York, NY, USA
e
Mayo Clinic, Rochester, MN, USA
f
RadPharm, Princeton, NJ, USA
g
Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD, USA
h
Schering-Plough, Kenilworth, NJ, USA
i
East Surrey Hospital, Redhill, Surrey, UK
j
National Cancer Research Network, Leeds, UK
k
Erasmus University Medical Center, Rotterdam, The Netherlands
b
A R T I C L E I N F O
A B S T R A C T
Article history:
Background: Assessment of the change in tumour burden is an important feature of the
Received 17 October 2008
clinical evaluation of cancer therapeutics: both tumour shrinkage (objective response)
Accepted 29 October 2008
and disease progression are useful endpoints in clinical trials. Since RECIST was published
in 2000, many investigators, cooperative groups, industry and government authorities have
adopted these criteria in the assessment of treatment outcomes. However, a number of
Keywords:
questions and issues have arisen which have led to the development of a revised RECIST
Response criteria
guideline (version 1.1). Evidence for changes, summarised in separate papers in this special
Solid tumours
issue, has come from assessment of a large data warehouse (>6500 patients), simulation
Guidelines
studies and literature reviews.

Highlights of revised RECIST 1.1: Major changes include: Number of lesions to be assessed: based
on evidence from numerous trial databases merged into a data warehouse for analysis purposes, the number of lesions required to assess tumour burden for response determination
has been reduced from a maximum of 10 to a maximum of five total (and from five to two
per organ, maximum). Assessment of pathological lymph nodes is now incorporated: nodes
with a short axis of P15 mm are considered measurable and assessable as target lesions.
The short axis measurement should be included in the sum of lesions in calculation of
tumour response. Nodes that shrink to <10 mm short axis are considered normal. Confirmation of response is required for trials with response primary endpoint but is no longer
required in randomised studies since the control arm serves as appropriate means of interpretation of data. Disease progression is clarified in several aspects: in addition to the previous definition of progression in target disease of 20% increase in sum, a 5 mm absolute
increase is now required as well to guard against over calling PD when the total sum is very
* Corresponding author: Tel.: +1 613 533 6430; fax: +1 613 533 2411.
E-mail address: [email protected] (E.A. Eisenhauer).
0959-8049/$ - see front matter 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.ejca.2008.10.026
4 5 ( 2 0 0 9 ) 2 2 8 2 4 7
229
small. Furthermore, there is guidance offered on what constitutes unequivocal progression of non-measurable/non-target disease, a source of confusion in the original RECIST
guideline. Finally, a section on detection of new lesions, including the interpretation of
FDG-PET scan assessment is included. Imaging guidance: the revised RECIST includes a
new imaging appendix with updated recommendations on the optimal anatomical assessment of lesions.
Future work: A key question considered by the RECIST Working Group in developing RECIST
1.1 was whether it was appropriate to move from anatomic unidimensional assessment of
tumour burden to either volumetric anatomical assessment or to functional assessment
with PET or MRI. It was concluded that, at present, there is not sufficient standardisation
or evidence to abandon anatomical assessment of tumour burden. The only exception to
this is in the use of FDG-PET imaging as an adjunct to determination of progression. As
is detailed in the final paper in this special issue, the use of these promising newer
approaches requires appropriate clinical validation studies.
2008 Elsevier Ltd. All rights reserved.
1.
Background
1.1.
History of RECIST criteria
Assessment of the change in tumour burden is an important

feature of the clinical evaluation of cancer therapeutics. Both
tumour shrinkage (objective response) and time to the development of disease progression are important endpoints in
cancer clinical trials. The use of tumour regression as the
endpoint for phase II trials screening new agents for evidence of anti-tumour effect is supported by years of evidence suggesting that, for many solid tumours, agents
which produce tumour shrinkage in a proportion of patients
have a reasonable (albeit imperfect) chance of subsequently
demonstrating an improvement in overall survival or other
time to event measures in randomised phase III studies (reviewed in [14]). At the current time objective response carries with it a body of evidence greater than for any other
biomarker supporting its utility as a measure of promising
treatment effect in phase II screening trials. Furthermore,
at both the phase II and phase III stage of drug development,
clinical trials in advanced disease settings are increasingly
utilising time to progression (or progression-free survival)
as an endpoint upon which efficacy conclusions are drawn,
which is also based on anatomical measurement of tumour
size.
However, both of these tumour endpoints, objective response and time to disease progression, are useful only if
based on widely accepted and readily applied standard criteria based on anatomical tumour burden. In 1981 the World
Health Organisation (WHO) first published tumour response
criteria, mainly for use in trials where tumour response was
the primary endpoint. The WHO criteria introduced the concept of an overall assessment of tumour burden by summing
the products of bidimensional lesion measurements and
determined response to therapy by evaluation of change from
baseline while on treatment.5 However, in the decades that
followed their publication, cooperative groups and pharmaceutical companies that used the WHO criteria often modified them to accommodate new technologies or to address
areas that were unclear in the original document. This led
to confusion in interpretation of trial results6 and in fact,

the application of varying response criteria was shown to lead
to very different conclusions about the efficacy of the same
regimen.7 In response to these problems, an International
Working Party was formed in the mid 1990s to standardise
and simplify response criteria. New criteria, known as RECIST
(Response Evaluation Criteria in Solid Tumours), were published in 2000.8 Key features of the original RECIST include
definitions of minimum size of measurable lesions, instructions on how many lesions to follow (up to 10; a maximum
five per organ site), and the use of unidimensional, rather
than bidimensional, measures for overall evaluation of tumour burden. These criteria have subsequently been widely
adopted by academic institutions, cooperative groups, and
industry for trials where the primary endpoints are objective
response or progression. In addition, regulatory authorities
accept RECIST as an appropriate guideline for these
assessments.
1.2.
Why update RECIST?
Since RECIST was published in 2000, many investigators have

confirmed in prospective analyses the validity of substituting
unidimensional for bidimensional (and even three-dimensional)-based criteria (reviewed in [9]). With rare exceptions
(e.g. mesothelioma), the use of unidimensional criteria seems
to perform well in solid tumour phase II studies.
However, a number of questions and issues have arisen
which merit answers and further clarity. Amongst these
are whether fewer than 10 lesions can be assessed without
affecting the overall assigned response for patients (or the
conclusion about activity in trials); how to apply RECIST in
randomised phase III trials where progression, not response,
is the primary endpoint particularly if not all patients have
measurable disease; whether or how to utilise newer imaging technologies such as FDG-PET and MRI; how to handle
assessment of lymph nodes; whether response confirmation
is truly needed; and, not least, the applicability of RECIST in
trials of targeted non-cytotoxic drugs. This revision of the
RECIST guidelines includes updates that touch on all these
points.
230
1.3.
Process of RECIST 1.1 development
The RECIST Working Group, consisting of clinicians with

expertise in early drug development from academic research
organisations, government and industry, together with imaging specialists and statisticians, has met regularly to set the
agenda for an update to RECIST, determine the evidence
needed to justify the various changes made, and to review
emerging evidence. A critical aspect of the revision process
was to create a database of prospectively documented solid
tumour measurement data obtained from industry and academic group trials. This database, assembled at the EORTC
Data Centre under the leadership of Jan Bogaerts and Patrick
Therasse (co-authors of this guideline), consists of >6500 patients with >18,000 target lesions and was utilised to investigate the impact of a variety of questions (e.g. number of
target lesions required, the need for response confirmation,
and lymph node measurement rules) on response and progression-free survival outcomes. The results of this work,
which after evaluation by the RECIST Working Group led to
most of the changes in this revised guideline, are reported
in detail in a separate paper in this special issue.10 Larry Schwartz and Robert Ford (also co-authors of this guideline) also
provided key databases from which inferences have been
made that inform these revisions.11
The publication of this revised guideline is believed to be
timely since it incorporates changes to simplify, optimise
and standardise the assessment of tumour burden in clinical
trials. A summary of key changes is found in Appendix I. Because the fundamental approach to assessment remains
grounded in the anatomical, rather than functional, assessment of disease, we have elected to name this version RECIST
1.1, rather than 2.0.
1.4.
What about volumetric or functional assessment?
This raises the question, frequently posed, about whether it is

time to move from anatomic unidimensional assessment of
tumour burden to either volumetric anatomical assessment
or to functional assessment (e.g. dynamic contrast enhanced
MRI or CT or (18)F-fluorodeoxyglucose positron emission
tomographic (FDG-PET) techniques assessing tumour metabolism). As can be seen, the Working Group and particularly
those involved in imaging research, did not believe that there
is at present sufficient standardisation and widespread availability to recommend adoption of these alternative assessment methods. The only exception to this is in the use of
FDG-PET imaging as an adjunct to determination of progression, as described later in this guideline. As detailed in paper
in this special issue12, we believe that the use of these promising newer approaches (which could either add to or substitute
for anatomical assessment as described in RECIST) requires
appropriate and rigorous clinical validation studies. This paper by Sargent et al. illustrates the type of data that will be
needed to be able to define endpoints for these modalities
and how to determine where and when such criteria/modalities can be used to improve the reliability with which truly
active new agents are identified and truly inactive new agents
are discarded in comparison to RECIST criteria in phase II
screening trials. The RECIST Working Group looks forward
4 5 ( 2 0 0 9 ) 2 2 8 2 4 7
to such data emerging in the next few years to allow the

appropriate changes to the next iteration of the RECIST
criteria.
2.
Purpose of this guideline
This guideline describes a standard approach to solid tumour

measurement and definitions for objective assessment of
change in tumour size for use in adult and paediatric cancer
clinical trials. It is expected these criteria will be useful in all
trials where objective response is the primary study endpoint,
as well as in trials where assessment of stable disease, tumour progression or time to progression analyses are undertaken, since all of these outcome measures are based on an
assessment of anatomical tumour burden and its change on
study. There are no assumptions in this paper about the proportion of patients meeting the criteria for any of these endpoints which will signal that an agent or treatment regimen is
active: those definitions are dependent on type of cancer in
which a trial is being undertaken and the specific agent(s) under study. Protocols must include appropriate statistical sections which define the efficacy parameters upon which the
trial sample size and decision criteria are based. In addition
to providing definitions and criteria for assessment of tumour
response, this guideline also makes recommendations
regarding standard reporting of the results of trials that utilise
tumour response as an endpoint.
While these guidelines may be applied in malignant brain
tumour studies, there are also separate criteria published for
response assessment in that setting.13 This guideline is not intended for use for studies of malignant lymphoma since
international guidelines for response assessment in lymphoma are published separately.14
Finally, many oncologists in their daily clinical practice follow their patients malignant disease by means of repeated
imaging studies and make decisions about continued therapy
on the basis of both objective and symptomatic criteria. It is
not intended that these RECIST guidelines play a role in that
decision making, except if determined appropriate by the
treating oncologist.
3.
Measurability of tumour at baseline
3.1.
Definitions
At baseline, tumour lesions/lymph nodes will be categorised

measurable or non-measurable as follows:
3.1.1.
Measurable
Tumour lesions: Must be accurately measured in at least one

dimension (longest diameter in the plane of measurement is
to be recorded) with a minimum size of:
10 mm by CT scan (CT scan slice thickness no greater than
5 mm; see Appendix II on imaging guidance).
10 mm caliper measurement by clinical exam (lesions
which cannot be accurately measured with calipers should
be recorded as non-measurable).
20 mm by chest X-ray.
Malignant lymph nodes: To be considered pathologically enlarged and measurable, a lymph node must be P15 mm in
short axis when assessed by CT scan (CT scan slice thickness
recommended to be no greater than 5 mm). At baseline and in
follow-up, only the short axis will be measured and followed
(see Schwartz et al. in this Special Issue15). See also notes below on Baseline documentation of target and non-target lesions for information on lymph node measurement.
3.1.2.
Non-measurable
All other lesions, including small lesions (longest diameter

<10 mm or pathological lymph nodes with P10 to <15 mm
short axis) as well as truly non-measurable lesions. Lesions
considered truly non-measurable include: leptomeningeal disease, ascites, pleural or pericardial effusion, inflammatory
breast disease, lymphangitic involvement of skin or lung,
abdominal masses/abdominal organomegaly identified by
physical exam that is not measurable by reproducible imaging
techniques.
3.1.3.
Special considerations regarding lesion measurability
Bone lesions, cystic lesions, and lesions previously treated

with local therapy require particular comment:
Bone lesions:.
Bone scan, PET scan or plain films are not considered adequate imaging techniques to measure bone lesions. However, these techniques can be used to confirm the
presence or disappearance of bone lesions.
Lytic bone lesions or mixed lytic-blastic lesions, with identifiable soft tissue components, that can be evaluated by cross
sectional imaging techniques such as CT or MRI can be considered as measurable lesions if the soft tissue component
meets the definition of measurability described above.
Blastic bone lesions are non-measurable.
Cystic lesions:.
Lesions that meet the criteria for radiographically defined
simple cysts should not be considered as malignant lesions
(neither measurable nor non-measurable) since they are, by
definition, simple cysts.
Cystic lesions thought to represent cystic metastases can
be considered as measurable lesions, if they meet the definition of measurability described above. However, if noncystic lesions are present in the same patient, these are preferred for selection as target lesions.
Lesions with prior local treatment:.

Tumour lesions situated in a previously irradiated area, or
in an area subjected to other loco-regional therapy, are usually not considered measurable unless there has been demonstrated progression in the lesion. Study protocols should
detail the conditions under which such lesions would be
considered measurable.
3.2.
Specifications by methods of measurements
3.2.1.
Measurement of lesions
All measurements should be recorded in metric notation,

using calipers if clinically assessed. All baseline evaluations
4 5 ( 2 0 0 9 ) 2 2 8 2 4 7
231
should be performed as close as possible to the treatment

start and never more than 4 weeks before the beginning of
the treatment.
3.2.2.
Method of assessment
The same method of assessment and the same technique

should be used to characterise each identified and reported
lesion at baseline and during follow-up. Imaging based evaluation should always be done rather than clinical examination
unless the lesion(s) being followed cannot be imaged but are
assessable by clinical exam.
Clinical lesions: Clinical lesions will only be considered measurable when they are superficial and P10 mm diameter as
assessed using calipers (e.g. skin nodules). For the case of skin
lesions, documentation by colour photography including a ruler to estimate the size of the lesion is suggested. As noted
above, when lesions can be evaluated by both clinical exam
and imaging, imaging evaluation should be undertaken since
it is more objective and may also be reviewed at the end of the
study.
Chest X-ray: Chest CT is preferred over chest X-ray, particularly when progression is an important endpoint, since CT is
more sensitive than X-ray, particularly in identifying new lesions. However, lesions on chest X-ray may be considered
measurable if they are clearly defined and surrounded by aerated lung. See Appendix II for more details.
CT, MRI: CT is the best currently available and reproducible
method to measure lesions selected for response assessment.
This guideline has defined measurability of lesions on CT
scan based on the assumption that CT slice thickness is
5 mm or less. As is described in Appendix II, when CT scans
have slice thickness greater than 5 mm, the minimum size
for a measurable lesion should be twice the slice thickness.
MRI is also acceptable in certain situations (e.g. for body
scans). More details concerning the use of both CT and MRI
for assessment of objective tumour response evaluation are
provided in Appendix II.
Ultrasound: Ultrasound is not useful in assessment of lesion
size and should not be used as a method of measurement.
Ultrasound examinations cannot be reproduced in their entirety for independent review at a later date and, because
they are operator dependent, it cannot be guaranteed that
the same technique and measurements will be taken from
one assessment to the next (described in greater detail in
Appendix II). If new lesions are identified by ultrasound in
the course of the study, confirmation by CT or MRI is advised. If there is concern about radiation exposure at CT,
MRI may be used instead of CT in selected instances.
Endoscopy, laparoscopy: The utilisation of these techniques for
objective tumour evaluation is not advised. However, they
can be useful to confirm complete pathological response
when biopsies are obtained or to determine relapse in trials
where recurrence following complete response or surgical
resection is an endpoint.
Tumour markers: Tumour markers alone cannot be used to assess objective tumour response. If markers are initially above
232
the upper normal limit, however, they must normalise for a

patient to be considered in complete response. Because
tumour markers are disease specific, instructions for their
measurement should be incorporated into protocols on a
disease specific basis. Specific guidelines for both CA-125
response (in recurrent ovarian cancer) and PSA response (in
recurrent prostate cancer), have been published.1618 In addition, the Gynecologic Cancer Intergroup has developed CA125
progression criteria which are to be integrated with objective
tumour assessment for use in first-line trials in ovarian
cancer.19
Cytology, histology: These techniques can be used to differentiate between PR and CR in rare cases if required by protocol
(for example, residual lesions in tumour types such as germ
cell tumours, where known residual benign tumours can remain). When effusions are known to be a potential adverse
effect of treatment (e.g. with certain taxane compounds or
angiogenesis inhibitors), the cytological confirmation of the
neoplastic origin of any effusion that appears or worsens during treatment can be considered if the measurable tumour
has met criteria for response or stable disease in order to differentiate between response (or stable disease) and progressive disease.
4.
Tumour response evaluation
4.1.
Assessment of overall tumour burden and
measurable disease
To assess objective response or future progression, it is necessary to estimate the overall tumour burden at baseline and
use this as a comparator for subsequent measurements.
Only patients with measurable disease at baseline should
be included in protocols where objective tumour response
is the primary endpoint. Measurable disease is defined by
the presence of at least one measurable lesion (as detailed
above in Section 3). In studies where the primary endpoint
is tumour progression (either time to progression or proportion with progression at a fixed date), the protocol must
specify if entry is restricted to those with measurable disease
or whether patients having non-measurable disease only are
also eligible.
4.2.
Baseline documentation of target and non-target
lesions
When more than one measurable lesion is present at baseline
all lesions up to a maximum of five lesions total (and a maximum of two lesions per organ) representative of all involved
organs should be identified as target lesions and will be recorded and measured at baseline (this means in instances
where patients have only one or two organ sites involved a
maximum of two and four lesions respectively will be recorded). For evidence to support the selection of only five target lesions, see analyses on a large prospective database in
the article by Bogaerts et al.10.
Target lesions should be selected on the basis of their size
(lesions with the longest diameter), be representative of all in-
4 5 ( 2 0 0 9 ) 2 2 8 2 4 7
volved organs, but in addition should be those that lend

themselves to reproducible repeated measurements. It may be
the case that, on occasion, the largest lesion does not lend itself to reproducible measurement in which circumstance the
next largest lesion which can be measured reproducibly
should be selected. To illustrate this point see the example
in Fig. 3 of Appendix II.
Lymph nodes merit special mention since they are normal
anatomical structures which may be visible by imaging even
if not involved by tumour. As noted in Section 3, pathological
nodes which are defined as measurable and may be identified as target lesions must meet the criterion of a short axis
of P15 mm by CT scan. Only the short axis of these nodes
will contribute to the baseline sum. The short axis of the
node is the diameter normally used by radiologists to judge
if a node is involved by solid tumour. Nodal size is normally
reported as two dimensions in the plane in which the image
is obtained (for CT scan this is almost always the axial plane;
for MRI the plane of acquisition may be axial, saggital or
coronal). The smaller of these measures is the short axis.
For example, an abdominal node which is reported as being
20 mm 30 mm has a short axis of 20 mm and qualifies as a
malignant, measurable node. In this example, 20 mm should
be recorded as the node measurement (See also the example
in Fig. 4 in Appendix II). All other pathological nodes (those
with short axis P10 mm but <15 mm) should be considered
non-target lesions. Nodes that have a short axis <10 mm
are considered non-pathological and should not be recorded
or followed.
A sum of the diameters (longest for non-nodal lesions, short
axis for nodal lesions) for all target lesions will be calculated
and reported as the baseline sum diameters. If lymph nodes
are to be included in the sum, then as noted above, only the
short axis is added into the sum. The baseline sum diameters
will be used as reference to further characterise any objective
tumour regression in the measurable dimension of the
disease.
All other lesions (or sites of disease) including pathological
lymph nodes should be identified as non-target lesions and
should also be recorded at baseline. Measurements are not required and these lesions should be followed as present, absent, or in rare cases unequivocal progression (more details
to follow). In addition, it is possible to record multiple nontarget lesions involving the same organ as a single item on
the case record form (e.g. multiple enlarged pelvic lymph
nodes or multiple liver metastases).
4.3.
Response criteria
This section provides the definitions of the criteria used to

determine objective tumour response for target lesions.
4.3.1.
Evaluation of target lesions
Complete Response (CR): Disappearance of all target lesions.

Any pathological lymph nodes (whether target or
non-target) must have 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.
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 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).
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.
4.3.2. Special notes on the assessment of target lesions

Lymph nodes. Lymph nodes identified as target lesions should
always have the actual short axis measurement recorded (measured in the same anatomical plane as the baseline examination), even if the nodes regress to below 10 mm on study. This
means that when lymph nodes are included as target lesions,
the sum of lesions may not be zero even if complete response
criteria are met, since a normal lymph node is defined as having
a short axis of <10 mm. Case report forms or other data collection methods may therefore be designed to have target nodal lesions recorded in a separate section where, in order to qualify
for CR, each node must achieve a short axis <10 mm. For PR,
SD and PD, the actual short axis measurement of the nodes is
to be included in the sum of target lesions.
Target lesions that become too small to measure. While on

study, all lesions (nodal and non-nodal) recorded at baseline
should have their actual measurements recorded at each subsequent evaluation, even when very small (e.g. 2 mm). However, sometimes lesions or lymph nodes which are recorded
as target lesions at baseline become so faint on CT scan that
the radiologist may not feel comfortable assigning an exact
measure and may report them as being too small to measure.
When this occurs it is important that a value be recorded on
the case report form. If it is the opinion of the radiologist that
the lesion has likely disappeared, the measurement should be
recorded as 0 mm. If the lesion is believed to be present and is
faintly seen but too small to measure, a default value of 5 mm
should be assigned (Note: It is less likely that this rule will be
used for lymph nodes since they usually have a definable size
when normal and are frequently surrounded by fat such as in
the retroperitoneum; however, if a lymph node is believed to
be present and is faintly seen but too small to measure, a default value of 5 mm should be assigned in this circumstance as
well). This default value is derived from the 5 mm CT slice
thickness (but should not be changed with varying CT slice
thickness). The measurement of these lesions is potentially
non-reproducible, therefore providing this default value will
prevent false responses or progressions based upon measurement error. To reiterate, however, if the radiologist is able to
provide an actual measure, that should be recorded, even if
it is below 5 mm.
Lesions that split or coalesce on treatment. As noted in Appendix II, when non-nodal lesions fragment, the longest diameters of the fragmented portions should be added together to
calculate the target lesion sum. Similarly, as lesions coalesce,
a plane between them may be maintained that would aid in
4 5 ( 2 0 0 9 ) 2 2 8 2 4 7
233
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.
4.3.3.
Evaluation of non-target lesions
This section provides the definitions of the criteria used to determine the tumour response for the group 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 (see comments below) of existing non-target lesions. (Note:
the appearance of one or more new lesions is also
considered progression).
4.3.4. Special notes on assessment of progression of nontarget disease

The concept of progression of non-target disease requires
additional explanation as follows:
When the patient also has measurable disease. In this setting,

to achieve unequivocal progression on the basis of the
non-target disease, there must be an overall level of substantial worsening in non-target disease such that, even in presence of SD or PR in target disease, the overall tumour
burden has increased sufficiently to merit discontinuation
of therapy (see examples in Appendix II and further details
below). A modest increase in the size of one or more non-target lesions is usually not sufficient to quality for unequivocal
progression status. The designation of overall progression solely on the basis of change in non-target disease in the face of
SD or PR of target disease will therefore be extremely rare.
When the patient has only non-measurable disease. This circumstance arises in some phase III trials when it is not a criterion of
study entry to have measurable disease. The same general concepts apply here as noted above, however, in this instance there
is no measurable disease assessment to factor into the interpretation of an increase in non-measurable disease burden.
Because worsening in non-target disease cannot be easily
quantified (by definition: if all lesions are truly non-measurable) a useful test that can be applied when assessing patients
for unequivocal progression is to consider if the increase in
overall disease burden based on the change in non-measurable
disease is comparable in magnitude to the increase that would
be required to declare PD for measurable disease: i.e. an increase
in tumour burden representing an additional 73% increase in
volume (which is equivalent to a 20% increase diameter in a
measurable lesion). Examples include an increase in a pleural
effusion from trace to large, an increase in lymphangitic
234
disease from localised to widespread, or may be described in

protocols as sufficient to require a change in therapy. Some
illustrative examples are shown in Figs. 5 and 6 in Appendix II.
If unequivocal progression is seen, the patient should be considered to have had overall PD at that point. While it would be
ideal to have objective criteria to apply to non-measurable disease, the very nature of that disease makes it impossible to do
so, therefore the increase must be substantial.
4.3.5.
New lesions
The appearance of new malignant lesions denotes disease

progression; therefore, some comments on detection of new
lesions are important. There are no specific criteria for the
identification of new radiographic lesions; however, the finding of a new lesion should be unequivocal: i.e. not attributable
to differences in scanning technique, change in imaging
modality or findings thought to represent something other
than tumour (for example, some new bone lesions may be
simply healing or flare of pre-existing lesions). This is particularly important when the patients baseline lesions show
partial or complete response. For example, necrosis of a liver
lesion may be reported on a CT scan report as a new cystic
lesion, which it is not.
A lesion identified on a follow-up study in an anatomical
location that was not scanned at baseline is considered a new
lesion and will indicate disease progression. An example of this
is the patient who has visceral disease at baseline and while on
study has a CT or MRI brain ordered which reveals metastases.
The patients brain metastases are considered to be evidence of
PD even if he/she did not have brain imaging at baseline.
If a new lesion is equivocal, for example because of its
small size, continued therapy and follow-up evaluation will
clarify if it represents truly new disease. If repeat scans confirm there is definitely a new lesion, then progression should
be declared using the date of the initial scan.
While FDG-PET response assessments need additional
study, it is sometimes reasonable to incorporate the use of
FDG-PET scanning to complement CT scanning in assessment
of progression (particularly possible new disease). New lesions on the basis of FDG-PET imaging can be identified
according to the following algorithm:
a. Negative FDG-PET at baseline, with a positivel FDG-PET
at follow-up is a sign of PD based on a new lesion.
b. No FDG-PET at baseline and a positive FDG-PET at follow-up:
If the positive FDG-PET at follow-up corresponds to a
new site of disease confirmed by CT, this is PD.
If the positive FDG-PET at follow-up is not confirmed as
a new site of disease on CT, additional follow-up CT
scans are needed to determine if there is truly progression occurring at that site (if so, the date of PD will be
the date of the initial abnormal FDG-PET scan).
If the positive FDG-PET at follow-up corresponds to a
pre-existing site of disease on CT that is not progressing on the basis of the anatomic images, this is not PD.
l
A positive FDG-PET scan lesion means one which is FDG avid

with an uptake greater than twice that of the surrounding tissue
on the attenuation corrected image.
4 5 ( 2 0 0 9 ) 2 2 8 2 4 7
4.4.
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. On occasion a response may not be documented until after the end
of therapy so protocols should be clear if post-treatment
assessments are to be considered in determination of best
overall response. Protocols must specify how any new therapy
introduced before progression will affect best response designation. The patients 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 (see Section 4.6). Specifically, in non-randomised trials where response is the primary endpoint,
confirmation of PR or CR is needed to deem either one the
best overall response. This is described further below.
4.4.1.
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.
When patients have non-measurable (therefore non-target) disease only, Table 2 is to be used.
4.4.2.
Missing assessments and inevaluable designation
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. For example, 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.
4.4.3.
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 (for
example, 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 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 patients best response
depends on the subsequent assessments. For example, a patient who has SD at first assessment, PD at second and does
not meet minimum duration for SD, will have a best response
of PD. The same patient lost to follow-up after the first SD
assessment would be considered inevaluable.
Table 1 Time point response: patients with target (+/

non-target) disease.
Target lesions Non-target lesions
CR
CR
CR
PR
SD
Not all
evaluated
PD
Any
Any
New
lesions
Overall
response
CR
Non-CR/non-PD
Not evaluated
Non-PD or
not all evaluated
Non-PD or
not all evaluated
Non-PD
No
No
No
No
CR
PR
PR
PR
No
SD
No
NE
Any
PD
Any
Yes or No
Yes or No
Yes
PD
PD
PD
CR = complete response, PR = partial response, SD = stable disease,

PD = progressive disease, and NE = inevaluable.
Table 2 Time point response: patients with non-target

disease only.
Non-target lesions
CR
Non-CR/non-PD
Not all evaluated
Unequivocal PD
Any
New lesions
Overall response
No
No
No
Yes or No
Yes
CR
Non-CR/non-PDa
NE
PD
PD
CR = complete
response,
PD = progressive
disease,
and
NE = inevaluable.
a Non-CR/non-PD is preferred over stable disease for non-target
disease since SD is increasingly used as endpoint for assessment
of efficacy in some trials so to assign this category when no
lesions can be measured is not advised.
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
4 5 ( 2 0 0 9 ) 2 2 8 2 4 7
235
at a subsequent time point as specified in the protocol (generally 4 weeks later). In this circumstance, the best overall response can be interpreted as in Table 3.
4.4.4.
Special notes on response assessment
When nodal disease is included in the sum of target lesions

and the nodes decrease to normal size (<10 mm), they may
still have a measurement reported on scans. This measurement should be recorded even though the nodes are normal
in order not to overstate progression should it be based on
increase in size of the nodes. As noted earlier, this means that
patients with CR may not have a total sum of zero on the
case report form (CRF).
In trials where confirmation of response is required, repeated NE time point assessments may complicate best response determination. The analysis plan for the trial must
address how missing data/assessments will be addressed in
determination of response and progression. For example, in
most trials it is reasonable to consider a patient with time
point responses of PR-NE-PR as a confirmed response.
Patients with a global deterioration of health status requiring discontinuation of treatment without objective evidence
of disease progression at that time should be reported as
symptomatic deterioration. Every effort should be made to
document objective progression even after discontinuation
of treatment. Symptomatic deterioration is not a descriptor
of an objective response: it is a reason for stopping study therapy. The objective response status of such patients is to be
determined by evaluation of target and non-target disease
as shown in Tables 13.
Conditions that define early progression, early death and
inevaluability are study specific and should be clearly described in each protocol (depending on treatment duration,
treatment periodicity).
In some circumstances it may be difficult to distinguish
residual disease from normal tissue. When the evaluation of
complete response depends upon this determination, it is
recommended that the residual lesion be investigated (fine
Table 3 Best overall response when confirmation of CR and PR required.

Overall response
First time point
CR
CR
CR
CR
CR
PR
PR
PR
PR
PR
NE
Overall response
Subsequent time point
CR
PR
SD
PD
NE
CR
PR
SD
PD
NE
NE
BEST overall response

CR
SD, PD or PRa
SD provided minimum
SD provided minimum
SD provided minimum
PR
PR
SD
SD provided minimum
SD provided minimum
NE
criteria for SD duration met, otherwise, PD

criteria for SD duration met, otherwise NE

criteria for SD duration met, otherwise NE
CR = complete response, PR = partial response, SD = stable disease, PD = progressive disease, and NE = inevaluable.
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.
236
needle aspirate/biopsy) before assigning a status of complete

response. FDG-PET may be used to upgrade a response to a CR
in a manner similar to a biopsy in cases where a residual
radiographic abnormality is thought to represent fibrosis or
scarring. The use of FDG-PET in this circumstance should be
prospectively described in the protocol and supported by disease specific medical literature for the indication. However, it
must be acknowledged that both approaches may lead to
false positive CR due to limitations of FDG-PET and biopsy resolution/sensitivity.
For equivocal findings of progression (e.g. very small and
uncertain new lesions; cystic changes or necrosis in existing
lesions), treatment may continue until the next scheduled
assessment. If at the next scheduled assessment, progression
is confirmed, the date of progression should be the earlier
date when progression was suspected.
4.5.
Frequency of tumour re-evaluation
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 68 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. Normally, all target and non-target
sites are evaluated at each assessment. In selected circumstances certain non-target organs may be evaluated less frequently. For example, bone scans may need to be repeated
only when complete response is identified in target disease
or when progression in bone is suspected.
After the end of the treatment, the need for repetitive tumour evaluations depends on whether the trial has as a goal
the response rate or the time to an event (progression/death).
If time to an event (e.g. time to progression, disease-free
survival, progression-free survival) is the main endpoint of
the study, then routine scheduled re-evaluation of protocol
specified sites of disease is warranted. In randomised comparative trials in particular, the scheduled assessments
should be performed as identified on a calendar schedule
(for example: every 68 weeks on treatment or every 34
months after treatment) and should not be affected by delays
in therapy, drug holidays or any other events that might lead
to imbalance in a treatment arm in the timing of disease
assessment.
4.6.
Confirmatory measurement/duration of response
4.6.1.
Confirmation
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.
This will also permit appropriate interpretation of results in
the context of historical data where response has traditionally
required confirmation in such trials (see the paper by Bogaerts
et al. in this Special Issue10). However, in all other circum-
4 5 ( 2 0 0 9 ) 2 2 8 2 4 7
stances, i.e. 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 central review to protect against bias, in particular in studies which are not blinded.
In the case of SD, measurements must have met the SD
criteria at least once after study entry at a minimum interval
(in general not less than 68 weeks) that is defined in the
study protocol.
4.6.2.
Duration of overall response
The duration of overall response is measured from the time

measurement criteria are first met for CR/PR (whichever is first
recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded on study).
The duration of overall complete response is measured
from the time measurement criteria are first met for CR until
the first date that recurrent disease is objectively documented.
4.6.3.
Duration of stable disease
Stable disease is measured from the start of the treatment (in

randomised trials, from date of randomisation) until the criteria for progression are met, taking as reference the smallest
sum on study (if the baseline sum is the smallest, this is the
reference for calculation of PD).
The clinical relevance of the duration of stable disease varies in different studies and diseases. If the proportion of patients achieving stable disease for a minimum period of time
is an endpoint of importance in a particular trial, the protocol
should specify the minimal time interval required between
two measurements for determination of stable disease.
Note: The duration of response and stable disease as well as
the progression-free survival are influenced by the frequency of
follow-up after baseline evaluation. It is not in the scope of this
guideline to define a standard follow-up frequency. The frequency should take into account many parameters including
disease types and stages, treatment periodicity and standard
practice. However, these limitations of the precision of the
measured endpoint should be taken into account if comparisons between trials are to be made.
4.7.
Progression-free survival/proportion progression-free
4.7.1.
Phase II trials
This guideline is focused primarily on the use of objective response endpoints for phase II trials. In some circumstances, response rate may not be the optimal method to assess the
potential anticancer activity of new agents/regimens. In such
cases progression-free survival (PFS) or the proportion progression-free at landmark time points, might be considered
appropriate alternatives to provide an initial signal of biologic
effect of new agents. It is clear, however, that in an uncontrolled
trial, these measures are subject to criticism since an apparently promising observation may be related to biological factors
such as patient selection and not the impact of the intervention.
Thus, phase II screening trials utilising these endpoints are best
designed with a randomised control. Exceptions may exist
where the behaviour patterns of certain cancers are so consistent (and usually consistently poor), that a non-randomised
trial is justifiable (see for example van Glabbeke et al.20). However, in these cases it will be essential to document with care
the basis for estimating the expected PFS or proportion progression-free in the absence of a treatment effect.
4.7.2.
Phase III trials
Phase III trials in advanced cancers are increasingly designed

to evaluate progression-free survival or time to progression as
the primary outcome of interest. Assessment of progression
is relatively straightforward if the protocol requires all patients to have measurable disease. However, restricting entry
to this subset of patients is subject to criticism: it may result
in a trial where the results are less likely to be generalisable if,
in the disease under study, a substantial proportion of patients would be excluded. Moreover, the restriction to entry
will slow recruitment to the study. Increasingly, therefore, trials allow entry of both patients with measurable disease as
well as those with non-measurable disease only. In this circumstance, care must be taken to explicitly describe the findings which would qualify for progressive disease for those
patients without measurable lesions. Furthermore, in this setting, protocols must indicate if the maximum number of recorded target lesions for those patients with measurable
disease may be relaxed from five to three (based on the data
found in Bogaerts et al.10 and Moskowitz et al.11). As found in
the special notes on assessment of progression, these guidelines offer recommendations for assessment of progression
in this setting. Furthermore, if available, validated tumour marker measures of progression (as has been proposed for ovarian
cancer) may be useful to integrate into the definition of progression. Centralised blinded review of imaging studies or of
source imaging reports to verify unequivocal progression
may be needed if important drug development or drug approval decisions are to be based on the study outcome. Finally,
as noted earlier, because the date of progression is subject to
ascertainment bias, timing of investigations in study arms
should be the same. The article by Dancey et al. in this special
issue21 provides a more detailed discussion of the assessment
of progression in randomised trials.
4.8.
Independent review of response and progression
For trials where objective response (CR + PR) is the primary endpoint, and in particular where key drug development decisions are based on the observation of a minimum number of
responders, it is recommended that all claimed responses be
reviewed by an expert(s) independent of the study. If the study
is a randomised trial, ideally reviewers should be blinded to
treatment assignment. Simultaneous review of the patients
files and radiological images is the best approach.
Independent review of progression presents some more
complex issues: for example, there are statistical problems
with the use of central-review-based progression time in
place of investigator-based progression time due to the potential introduction of informative censoring when the former
precedes the latter. An overview of these factors and other
lessons learned from independent review is provided in an
article by Ford et al. in this special issue.22
4 5 ( 2 0 0 9 ) 2 2 8 2 4 7
4.9.
Reporting best response results
4.9.1.
Phase II trials
237
When response is the primary endpoint, and thus all patients

must have measurable disease to enter the trial, all patients
included in the study must be accounted for in the report of
the results, even if there are major protocol treatment deviations or if they are not evaluable. Each patient will be assigned
one of the following categories:
1.
2.
3.
4.
5.
Complete response
Partial response
Stable disease
Progression
Inevaluable for response: specify reasons (for example: early
death, malignant disease; early death, toxicity; tumour
assessments not repeated/incomplete; other (specify)).
Normally, all eligible patients should be included in the

denominator for the calculation of the response rate for phase
II trials (in some protocols it will be appropriate to include all
treated patients). It is generally preferred that 95% two-sided
confidence limits are given for the calculated response rate.
Trial conclusions should be based on the response rate for
all eligible (or all treated) patients and should not be based
on a selected evaluable subset.
4.9.2.
Phase III trials
Response evaluation in phase III trials may be an indicator

of the relative anti-tumour activity of the treatments evaluated and is almost always a secondary endpoint. Observed differences in response rate may not predict the
clinically relevant therapeutic benefit for the population
studied. If objective response is selected as a primary endpoint for a phase III study (only in circumstances where a
direct relationship between objective tumour response and
a clinically relevant therapeutic benefit can be unambiguously demonstrated for the population studied), the same
criteria as those applying to phase II trials should be used
and all patients entered should have at least one measurable lesion.
In those many cases where response is a secondary endpoint and not all trial patients have measurable disease, the
method for reporting overall best response rates must be
pre-specified in the protocol. In practice, response rate may
be reported using either an intent to treat analysis (all randomised patients in the denominator) or an analysis where
only the subset of patients with measurable disease at
baseline are included. The protocol should clearly specify
how response results will be reported, including any subset
analyses that are planned.
The original version of RECIST suggested that in phase III
trials one could write protocols using a relaxed interpretation of the RECIST guidelines (for example, reducing the number of lesions measured) but this should no longer be done
since these revised guidelines have been amended in such a
way that it is clear how these criteria should be applied for
all trials in which anatomical assessment of tumour response
or progression are endpoints.
238
Appendix I. Summary of major changes RECIST 1.0 to RECIST 1.1

RECIST 1.0
Minimum size measurable
lesions
Rationale
CT: 10 mm spiral
20 mm non-spiral
CT 10 mm; delete reference to

spiral scan
Clinical: 20 mm
Clinical: 10 mm (must be
measurable with calipers)
CT:
P15 mm short axis for target
P10<15 mm for non-target
<10 mm is non-pathological
Most scans used have 5 mm or less slice

thickness Clearer to give instruction based on
slice interval if it is greater than 5 mm
Caliper measurement will make this reliable
Lymph node: not mentioned
Reference in special issue

(if applicable)
Since nodes are normal structure need to define

pathological enlargement. Short axis is most
sensitive
Schwartz et al.15
Notes included on bone

lesions, cystic lesions
Clarify frequently asked questions
Overall tumour burden
10 lesions (5 per organ)
5 lesions (2 per organ)
Data warehouse analysis shows no loss of

information if lesion number reduced from 10 to
5. A maximum of 2 lesions per organ yields
sufficient representation per disease site
Bogaerts et al.10
Response criteria target

disease
CR lymph node not mentioned
CR lymph nodes must be

<10 mm short axis
PD 20% increase over smallest
sum on study (including
baseline if that is smallest) and
at least 5 mm increase or new
lesions
In keeping with normal size of nodes
Schwartz et al.15
PD 20% increase over smallest sum on

study or new lesions
4 5 ( 2 0 0 9 ) 2 2 8 2 4 7
Special considerations on
lesion measurability
Clarification that if baseline measurement is

smaller than any on study measurement, it is
reference against which PD is assessed
5 mm absolute increase to guard against over
calling PD when total sum is very small and 20%
increase is within measurement error
Response criteria non-target

disease
unequivocal progression considered as PD
More detailed description of

unequivocal progression to
indicate that it should not
normally trump target disease
status. It must be
representative of overall
disease status change, not a
single lesion increase
Confusion with RECIST 1.0 where some were

considering PD if increase in any non-target
lesion, even when target disease is stable or
responding
New lesions
New section on New lesions
To provide guidance on when a lesion is

considered new (and thus PD)
Overall response
Table integrated target and non-target

lesions
Two tables: one integrating

target and non-target and the
other of non-target only
To account for the fact that RECIST criteria are

now being used in trials where PFS is the
endpoint and not all patients have measurable
(target) disease at baseline
RECIST 1.1
Dancey et al.21
RECIST 1.0
RECIST 1.1
Rationale
Special notes:
How to assess and measure
lymph nodes
CR in face of residual tissue
Discussion of equivocal
progression
Frequently asked questions on these topics
Reference in special issue

(if applicable)
Retain this requirement ONLY

for
non-randomised trials with
primary endpoint of response
Data warehouse shows that response rates

rise when confirmation is eliminated, but
the only circumstance where this is
important is in trials where there is no
concurrent comparative control and where
this measure is the primary endpoint
Bogaerts et al.10
Progression-free survival
General comments only
More specific comments on

use of PFS (or proportion
progression-free) as
phase II endpoint
Greater detail on PFS
assessment in phase III trials
Increasing use of PFS in phase III trials

requires guidance on assessment of PD in
patients with non-measurable disease
Dancey et al.21
Reporting of response
results
9 categories suggested for

reporting phase II results
Divided into phase II and phase

III
9 categories collapsed into 5
In phase III, guidance given
about reporting response
Simplifies reporting and clarifies how to

report phase II and III data consistently
Response in phase III

trials
More relaxed guidelines

possible if protocol specified
This section removed and

referenced in section
above: no need to have
different criteria for phase II
and III
Simplification of response assessment by

reducing number of lesions and eliminating
need for confirmation in randomised
studies where response is not the primary
endpoint makes separate rules
unnecessary
Imaging appendix
Appendix I
Appendix II: updated with

detailed guidance on
use of MRI, PET/CT
Other practical guidance
included
Evolving use of newer modalities addressed.

Enhanced guidance in response to frequent
questions and from radiology review
experience
New appendices
4 5 ( 2 0 0 9 ) 2 2 8 2 4 7
For CR and PR: criteria

must be met again 4
weeks after initial
documentation
Confirmatory measure
Appendix I: comparison of
RECIST 1.0 and 1.1
Appendix III: frequently asked
questions
239
240
Conflict of interest statement

None declared.
Acknowledgements
The RECIST Working Group would like to thank the following
organisations which made data bases available to us in order
to perform the analyses which informed decisions about
changes to this version of the criteria: Amgen; AstraZeneca;
Breast Cancer International Research Group (BCIRG); BristolMyers Squibb; European Organisation for Research and
Treatment of Cancer (EORTC) Breast Cancer Group and Gastrointestinal Group; Erasmus University Medical Center,
Rotterdam, The Netherlands; Genentech; Pfizer; RadPharm;
Roche; Sanofi Aventis.
We would also like to thank the following individuals from
academic, government, and pharmaceutical organisations for
providing helpful comments on an earlier draft of these revised
guidelines: Ohad Amit, Phil Murphy, Teri Crofts and Janet Begun, GlaxoSmithKline, USA; Laurence H. Baker, Southwest
Oncology Group, USA; Karla Ballman, Mayo Clinic, USA;
Charles Baum, Darrel Cohen, and Mary Ashford Collier, Pfizer,
USA; Gary J. Becker, American Board of Radiology, Tucson,
USA; Jean-Yves Blay, University Claude Pertrand, Lyon France;
Renzo Canetta, Bristol-Myers Squibb, USA; David Chang, Amgen Inc., USA; Sandra Chica, Perceptive Informations Inc. (PAREXEL), USA; Martin Edelman, University of Maryland
Greenbaum Cancer Centre, USA; Gwendolyn Fyfe, Genentech,
USA; Bruce Giantonio, Eastern Cooperative Oncology Group,
USA; Gary Gordon, Abbott Pharmaceuticals, USA; Ronald Gottlieb, Roswell Park Cancer Institute, USA; Simon Kao, University
of Iowa College of Medicine, USA; Wasaburo Koizumi, Kitasato
University, Japan; Alessandro Riva, Novartis Pharmaceuticals,
USA; Wayne Rackhoff, Ortho Biotech Oncology Research and
Development, USA; Nagahiro Saijo, President Japanese Society
of Medical Oncology, Japan; Mitchell Schnall American College
of Radiology Imaging Network, USA; Yoshik Shimamura, PAREXEL International Inc., Japan; Rajeshwari Sridhara, Centre
for Drug Evaluation and Research, Food and Drug Administration, USA; Andrew Stone, Alan Barge, AstraZeneca, United
Kingdom; Orhan Suleiman, Centre for Drug Evaluation and Research, Food and Drug Administration, USA; Daniel C. Sullivan,
Duke University Medical Centre, USA; Masakazu Toi, Kyoto
University, Japan; Cindy Welsh, Centre for Drug Evaluation
and Research, Food and Drug Administration, USA.
Finally, the RECIST Working Group would like to thank individuals who were not permanent members of the group (which
are all acknowledged as co-authors) but who attended working
group meetings from time to time and made contributions to
the total process over the past 7 years: Richard Pazdur, Food
and Drug Administration, USA; Francesco Pignatti, European
Medicines Agency, London, UK.
Appendix II. Specifications for standard

anatomical radiological imaging
These protocols for image acquisition of computed tomography (CT) and magnetic resonance imaging (MRI) are recom-
4 5 ( 2 0 0 9 ) 2 2 8 2 4 7
mendations intended for patients on clinical trials where

RECIST assessment will be performed. Standardisation of
imaging requirements and image acquisition parameters is
ideal to allow for optimal comparability of subjects within a
study and results between studies. These recommendations
are designed to balance optimised image acquisition protocols with techniques that should be feasible to perform globally at imaging facilities in all types of radiology practices.
These guidelines are not applicable to functional imaging
techniques or volumetric assessment of tumour size.
Scanner quality control is highly recommended and should
follow standard manufacturer and facility maintenance
schedules using commercial phantoms. It is likely that for RECIST unidimensional measurements this will be adequate to
produce reproducible measurements. Imaging quality control
for CT includes an analysis of image noise and uniformity and
CT number as well as spatial resolution. The frequency of
quality control analysis is also variable and should focus on
clinically relevant scanning parameters. Dose analysis is always important and the use of imaging should follow the
ALARA principle, As Low As Reasonably Achievable, which
refers to making every reasonable effort to maintain radiation
exposures as far below the dose limits as possible.
Specific.notes
Chest X-ray measurement of lesions surrounded by pulmonary parenchyma is feasible, but not preferable as the
measurement represents a summation of densities. Furthermore, there is poor identification of new lesions within the
chest on X-ray as compared with CT. Therefore, measurements of pulmonary parenchymal lesions as well as mediastinal disease are optimally performed with CT of the chest.
MRI of the chest should only be performed in extenuating circumstances. Even if IV contrast cannot be administered (for
example, in the situation of allergy to contrast), a non-contrast CT of the chest is still preferred over MRI or chest X-ray.
CT scans: CT scans of the chest, abdomen, and pelvis should
be contiguous throughout all the anatomic region of interest.
As a general rule, the minimum size of a measurable lesion at
baseline should be no less than double the slice thickness and
also have a minimum size of 10 mm (see below for minimum
size when scanners have a slice thickness more than 5 mm).
While the precise physics of lesion size and partial volume
averaging is complex, lesions smaller than 10 mm may be difficult to accurately and reproducibly measure. While this rule
is applicable to baseline scans, as lesions potentially decrease
in size at follow-up CT studies, they should still be measured.
Lesions which are reported as too small to measure should
be assigned a default measurement of 5 mm if they are still
visible.
The most critical CT image acquisition parameters for optimal tumour evaluation using RECIST are anatomic coverage,
contrast administration, slice thickness, and reconstruction interval.
a. Anatomic coverage: Optimal anatomic coverage for most
solid tumours is the chest, abdomen and pelvis. Coverage should encompass all areas of known predilection
for metastases in the disease under evaluation and
should additionally investigate areas that may be

involved based on signs and symptoms of individual
patients. Because a lesion later identified in a body part
not scanned at baseline would be considered as a new
lesion representing disease progression, careful consideration should be given to the extent of imaging coverage
at baseline and at subsequent follow-up time points.
This will enable better consistency not only of tumour
measurements but also identification of new disease.
b. IV contrast administration: Optimal visualisation and
measurement of metastases in solid tumours requires
consistent administration (dose and rate) of IV contrast
as well as timing of scanning. Typically, most abdominal imaging is performed during the portal venous
phase and (optimally) about the same time frame after
injection on each examination (see Fig. 1 for impact of
different phase of IV contrast on lesion measurement).
Most solid tumours may be scanned with a single
phase after administration of contrast. While triphasic
CT scans are sometimes performed on other types of
vascular tumours to improve lesion conspicuity, for
consistency and uniformity, we would recommend triphasic CT for hepatocellular and neuroendocrine
tumours for which this scanning protocol is generally
standard of care, and the improved temporal resolution
of the triphasic scan will enhance the radiologists ability to consistently and reproducibly measure these
lesions. The precise dose and rate of IV contrast is
dependent upon the CT scanning equipment, CT acquisition protocol, the type of contrast used, the available
venous access and the medical condition of the
patient. Therefore, the method of administration of
intravenous contrast agents is variable. Rather than
try to institute rigid rules regarding methods for
administering contrast agents and the volume injected,
it is appropriate to suggest that an adequate volume of
a suitable contrast agent should be given so that the
metastases are demonstrated to best effect and a consistent method is used on subsequent examinations for
any given patient (ideally, this would be specified in
the protocol or for an institution). It is very important
that the same technique be used at baseline and on fol-
4 5 ( 2 0 0 9 ) 2 2 8 2 4 7
241
low-up examinations for a given patient. This will

greatly enhance the reproducibility of the tumour measurements. If prior to enrolment it is known a patient is
not able to undergo CT scans with IV contrast due to
allergy or renal insufficiency, the decision as to
whether a non-contrast CT or MRI (with or without IV
contrast) should be used to evaluate the subject at
baseline and follow-up should be guided by the tumour
type under investigation and the anatomic location of
the disease. For patients who develop contraindications to contrast after baseline contrast CT is done,
the decision as to whether non-contrast CT or MRI
(enhanced or non-enhanced) should be performed
should also be based on the tumour type, anatomic
location of the disease and should be optimised to
allow for comparison to the prior studies if possible.
Each case should be discussed with the radiologist to
determine if substitution of these other approaches is
possible and, if not, the patient should be considered
not evaluable from that point forward. Care must be
taken in measurement of target lesions on a different
modality and interpretation of non-target disease or
new lesions, since the same lesion may appear to have
a different size using a new modality (see Fig. 2 for a
comparison of CT and MRI of the same lesion). Oral
contrast is recommended to help visualise and differentiate structures in the abdomen.
c. Slice thickness and reconstruction interval: RECIST measurements may be performed at most clinically obtained
slice thicknesses. It is recommended that CT scans be
performed at 5 mm contiguous slice thickness or less
and indeed this guideline presumes a minimum 5 mm
thickness in recommendations for measurable lesion
definition. Indeed, variations in slice thickness can have
an impact on lesion measurement and on detection of
new lesions. However, consideration should also be
given for minimising radiation exposure. With these
parameters, a minimum 10 mm lesion is considered
measurable at baseline. Occasionally, institutions may
perform medically acceptable scans at slice thicknesses
greater than 5 mm. If this occurs, the minimum size of
measurable lesions at baseline should be twice the slice
Fig. 1 Difference in measurement/visualisation with different phases of IV contrast administration. Hypervascular

metastases imaged in the arterial phase (left) and the portal venous phase (right). Note that the number of lesions visible
differs greatly between the two phases of contrast administration as does any potential lesion measurement. Consistent CT
scan acquisition, including phase of contrast administration, is important for optimal and reproducible tumour
242
4 5 ( 2 0 0 9 ) 2 2 8 2 4 7
Fig. 2 CT versus MRI of same lesions showing apparent progression due only to differing method of measurement.
thickness of the baseline scans. Most contemporary CT

scanners are multidetector which have many imaging
options for these acquisition parameters.23 The equipment vendor and scanning manual should be reviewed
if there are any specific system questions.
d. Alternative contrast agents: There are a number of other,
new contrast agents, some organ specific.24 They may
be used as part of patient care for instance, in liver
lesion assessment, or lymph node characterisation25,
but should not as yet be used in clinical trials.
FDG-PET has gained acceptance as a valuable tool for
detecting, staging and restaging several malignancies. Criteria
for incorporating (or substituting) FDG-PET into anatomical
assessment of tumour response in phase II trials are not yet
available, though much research is ongoing. Nevertheless,
FDG-PET is being used in many drug development trials both
as a tool to assess therapeutic efficacy and also in assessment
of progression. If FDG-PET scans are included in a protocol, by
consensus, an FDG uptake period of 60 min prior to imaging
has been decided as the most appropriate for imaging of patients with malignancy.26 Whole-body acquisition is important since this allows for sampling of all areas of interest
and can assess if new lesions have appeared thus determining
the possibility of interval progression of disease. Images from
the base of the skull to the level of the mid-thigh should be obtained 60 min post injection. PET camera specifications are
variable and manufacturer specific, so every attempt should
be made to use the same scanner, or the same model scanner,
for serial scans on the same patient. Whole-body acquisitions
can be performed in either 2- or 3-dimensional mode with
attenuation correction, but the method chosen should be consistent across all patients and serial scans in the clinical trial.
PET/CT scans: Combined modality scanning such as with
PETCT is increasingly used in clinical care, and is a modality/technology that is in rapid evolution; therefore, the recommendations in this paper may change rather quickly with
time. At present, low dose or attenuation correction CT portions of a combined PETCT are of limited use in anatomically
based efficacy assessments and it is therefore suggested that
they should not be substituted for dedicated diagnostic contrast enhanced CT scans for anatomically based RECIST measurements. However, if a site can document that the CT
performed as part of a PETCT is of identical diagnostic quality to a diagnostic CT (with IV and oral contrast) then the CT
portion of the PETCT can be used for RECIST measurements.
Note, however, that the PET portion of the CT introduces additional data which may bias an investigator if it is not routinely
or serially performed.
Ultrasound examinations should not be used in clinical trials
to measure tumour regression or progression of lesions because the examination is necessarily subjective and operator
dependent. The reasons for this are several: Entire examinations cannot be reproduced for independent review at a later
date, and it must be assumed, whether or not it is the case,
that the hard-copy films available represent a true and accurate reflection of events. Furthermore, if, for example, the
only measurable lesion is in the para-aortic region of the
abdomen and if gas in the bowel overlies the lesion, the lesion
will not be detected because the ultrasound beam cannot
penetrate the gas. Accordingly, the disease staging (or restaging for treatment evaluation) for this patient will not be
accurate.
While evaluation of lesions by physical examination is also
of limited reproducibility, it is permitted when lesions are
superficial, at least 10 mm size, and can be assessed using
calipers. In general, it is preferred if patients on clinical trials
have at least one lesion that is measurable by CT. Other skin
or palpable lesions may be measured on physical examination and be considered target lesions.
Use of MRI remains a complex issue. MRI has excellent
contrast, spatial and temporal resolution; however, there
are many image acquisition variables involved in MRI, which
greatly impact image quality, lesion conspicuity and measurement. Furthermore, the availability of MRI is variable
globally. As with CT, if an MRI is performed, the technical
specifications of the scanning sequences used should be
optimised for the evaluation of the type and site of disease.
Furthermore, as with CT, the modality used at follow-up
should be the same as was used at baseline and the lesions
should be measured/assessed on the same pulse sequence.
Generally, axial imaging of the abdomen and pelvis with T1
and T2 weighted imaging along with gadolinium enhanced
imaging should be performed. The field of view, matrix,
number of excitations, phase encode steps, use of fat suppression and fast sequences should be optimised for the spe-
cific body part being imaged as well as the scanner utilised. It

is beyond the scope of this document or appendix to prescribe specific MRI pulse sequence parameters for all scanners, body parts and diseases. Ideally, the same type of
scanner should be used and the image acquisition protocol
should be followed as closely as possible to prior scans. Body
scans should be performed with breath-hold scanning techniques if possible.
Selection of target lesions: In general, the largest lesions representative of involved organs (up to a maximum of two per
organ and five total) are selected to follow as target lesions.
However, in some cases, the largest lesions may not be easily
measured and are not suitable for follow-up because of their
configuration. In these cases, identification of the largest most
reproducible lesions is advised. Fig. 3 provides an illustrative
example where the largest lesion is not the most reproducible
and another lesion is better to select and follow:
Measurement of lesions
The longest diameter of selected lesions should be measured
in the plane in which the images were acquired. For body CT,
this is the axial plane. In the event isotropic reconstructions
are performed, measurements can be made on these reconstructed images; however, it should be cautioned that not
all radiology sites are capable of producing isotropic reconstructions. This could lead to the undesirable situation of
measurements in the axial plane at one assessment point
and in a different plane at a subsequent assessment. There
are some tumours, for instance paraspinal lesions, which
are better measured in the coronal or sagittal plane. It would
be acceptable to measure these lesions in these planes if the
4 5 ( 2 0 0 9 ) 2 2 8 2 4 7
243
reconstructions in those planes were isotropic or the images

were acquired with MRI in those planes. Using the same plane
of evaluation, the maximal diameter of each target lesion
should always be measured at subsequent follow-up time
points even if this results in measuring the lesion at a different slice level or in a different orientation or vector compared
with the baseline study. Software tools that calculate the
maximal diameter for a perimeter of a tumour may be employed and may even reduce variability.
The only exception to the longest diameter rule is lymph
node measurement. Because malignant nodes are identified
by the length of their short axis, this is the guide used to
determine not only whether they are pathological but is also
the dimension measured for adding into the sum of target lesions. Fig. 4 illustrates this point: the large arrow identifies a
malignant node: the shorter perpendicular axis is P15 mm
and will be recorded. Close by (small arrow) there is a normal
node: note here the long axis is greater than 10 mm but the
short axis is well below 10 mm. This node should be considered non-pathological.
If a lesion disappears and reappears at a subsequent time
point it should continue to be measured. However, the patients response at the point in time when the lesion reappears will depend upon the status of his/her other lesions.
For example, if the patients tumour had reached a CR status
and the lesion reappeared, then the patient would be considered PD at the time of reappearance. In contrast, if the tumour
status was a PR or SD and one lesion which had disappeared
then reappears, its maximal diameter should be added to the
sum of the remaining lesions for a calculated response: in
other words, the reappearance of an apparently disappeared
single lesion amongst many which remain is not in itself en-
Fig. 3 Largest lesion may not be most reproducible: most reproducible should be selected as target. In this example, the
primary gastric lesion (circled at baseline and at follow-up in the top two images) may be able to be measured with thin
section volumetric CT with the same degree of gastric distention at baseline and follow-up. However, this is potentially
challenging to reproduce in a multicentre trial and if attempted should be done with careful imaging input and analysis. The
most reproducible lesion is a lymph node (circled at baseline and at follow-up in the bottom two images).
244
Fig. 4 Lymph node assessment: large arrow illustrates a

pathological node with the short axis shown as a solid line
which should be measured and followed. Small arrow illustrates a non-pathological node which has a short axis
<10 mm.
4 5 ( 2 0 0 9 ) 2 2 8 2 4 7
ded in an organ with a similar contrast such as the liver, pancreas, kidney, adrenal or spleen. Additionally, peritumoural
oedema may surround a lesion and may be difficult to distinguish on certain modalities between this oedema and actual
tumour. In fact, pathologically, the presence of tumour cells
within the oedema region is variable. Therefore, it is most
critical that the measurements be obtained in a reproducible
manner from baseline and all subsequent follow-up timepoints. This is also a strong reason to consistently utilise
the same imaging modality.
When lesions fragment, the individual lesion diameters
should be added together to calculate the target lesion
sum. Similarly, as lesions coalesce, 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 merged
lesion.
Progression of non-target lesions

ough to qualify for PD: that requires the sum of all lesions to
meet the PD criteria. The rationale for such a categorisation is
based upon the realisation that most lesions do not actually
disappear but are not visualised because they are beyond
the resolving power of the imaging modality employed.
The identification of the precise boundary definition of a
lesion may be difficult especially when the lesion is embed-
To achieve unequivocal progression there must be an overall

level of substantial worsening in non-target disease that is of
a magnitude that, even in the presence of SD or PR in target
disease, the treating physician would feel it important to
change therapy. Examples of unequivocal progression are
shown in Figs. 5 and 6.
Fig. 5 Example of unequivocal progression in non-target lesions in liver.
Fig. 6 Example of unequivocal progression in non-target lesion (nodes).
245
4 5 ( 2 0 0 9 ) 2 2 8 2 4 7
Appendix III. Frequently asked questions

Question
Answer
What should be done if several unique lesions at

baseline become confluent at a follow-up
evaluation?
Measure the longest diameter of the confluent mass and record to add into the sum of
the longest diameters
How large does a new lesion have to be to count

as progression? Does any small subcentimetre
lesion qualify, or should the lesion be at least
measurable?
New lesions do not need to meet measurability criteria to be considered valid. If it is

clear on previous images (with the same technique) that a lesion was absent then its
definitive appearance implies progression. If there is any doubt (because of the
techniques or conditions) then it is suggested that treatment continue until next
scheduled assessment when, generally, all should be clear. Either it gets bigger and the
date of progression is the date of the first suspicion, or it disappears and one may then
consider it an artefact with the support of the radiologists
How should one lesion be measured if on

subsequent exams it is split into two?
Measure the longest diameter of each lesion and add this into the sum
Does the definition of progression depend on

the status of all target lesions or only one?
As per the RECIST 1.1 guideline, progression requires a 20% increase in the sum of
diameters of all target lesions AND a minimum absolute increase of 5 mm in the sum
Are RECIST criteria accepted by regulatory

agencies?
Many cooperative groups and members of pharma were involved in preparing RECIST
1.0 and have adopted them. The FDA was consulted in their development and supports
their use, though they dont require it. The European and Canadian regulatory
authorities also participated and the RECIST criteria are now integrated in the European
note for guidance for the development of anticancer agents. Many pharmaceutical
companies are also using them. RECIST 1.1 was similarly widely distributed before
publication
What is the criterion for a measurable lesion if

the CT slice thickness is >5 mm?
RECIST 1.1 recommends that CT scans have a maximum slice thickness of 5 mm and the
minimum size for a measurable lesion is twice that: 10 mm (even if slice thickness is
<5 mm). If scanners with slice thickness >5 mm are used, the minimum lesion size must
have a longest diameter twice the actual slice thickness
What should we record when target lesions

become so small they are below the 10 mm
measurable size?
Target lesion measurability is defined at baseline. Thereafter, actual measurements,

even if <10 mm, should be recorded. If lesions become very small, some radiologists
indicate they are too small to measure. This guideline advises that when this occurs, if
the lesion is actually still present, a default measurement of 5 mm should be applied. If
in fact the radiologist believes the lesion has gone, a default measurement of 0 mm
should be recorded
If a patient has several lesions which have

decreased in size to meet PR criteria and one
has actually disappeared, does that patient have
PD if the disappeared lesion reappears?
Unless the sum meets the PD criteria, the reappearance of a lesion in the setting of PR (or
SD) is not PD. The lesion should simply be added into the sum.
If the patients had had a CR, clearly reappearance of an absent lesion would qualify for
PD
When measuring the longest diameter of target

lesions in response to treatment, is the same
axis that was used initially used subsequently,
even if there is a shape change to the lesion that
may have produced a new longest diameter?
The longest diameter of the lesion should always be measured even if the actual axis is
different from the one used to measure the lesion initially (or at different time point
during follow-up)
The only exception to this is lymph nodes: as per RECIST 1.1 the short axis should
always be followed and as in the case of target lesions, the vector of the short axis may
change on follow-up
Target lesions have been selected at baseline

and followed but then one of these target
lesions then becomes non-evaluable (i.e.
different technique used)
What is the effect this has on the other target
lesions and the overall response?
What may be done in such cases is one of the following:

(a) If the patient is still being treated, call the centre to be sure that future evaluations are
done with the baseline technique so at least SOME courses are fully evaluable
(b) If that is not possible, check if there IS a baseline exam by the same technique which
was used to follow patients...in which case if you retrieve the baseline measures from
that technique you retrieve the lesion evaluability
(c) If neither (a) nor (b) is possible then it is a judgement call about whether you delete
the lesion from all forms or consider the impact of the lesion overall is so important that
its being non-evaluable makes the overall response interpretation inevaluable without
it. Such a decision should be discussed in a review panel
It is NOT recommended that the lesion be included in baseline sums and then excluded
from follow-up sums since this biases in favour of a response
(continued on next page)
246
4 5 ( 2 0 0 9 ) 2 2 8 2 4 7
Appendix III continued

Question
Answer
What if a single non-target lesion cannot be reviewed, for

whatever reason; does this negate the overall assessment?
Sometimes the major contribution of a single non-target lesion may be in

the setting of CR having otherwise been achieved: failure to examine one
non-target in that setting will leave you unable to claim CR. It is also
possible that the non-target lesion has undergone such substantial
progression that it would override the target disease and render patient
PD. However, this is very unlikely, especially if the rest of the measurable
disease is stable or responding
A patient has a 32% decrease in sum cycle 2, a 28% decrease cycle

4 and a 33% decrease cycle 6. Does confirmation of PR have to
take place in sequential scans or is a case like this confirmed PR?
It is not infrequent that tumour shrinkage hovers around the 30% mark.
In this case, most would consider PR to have been confirmed looking at
this overall case. Had there been two or three non-PR observations
between the two time point PR responses, the most conservative
approach would be to consider this case SD
In the setting of a breast cancer neoadjuvant study, would

mammography not be used to assess lesions? Is CT preferred in
this setting?
Neither CT nor mammography are optimal in this setting. MRI is the

preferred modality to follow breast lesions in a neoadjuvant setting
A patient has a lesion measurable by clinical exam and by CT

scan. Which should be followed?
CT scan. Always follow by imaging if that option exists since it can be

reviewed and verified
A lesion which was solid at baseline has become necrotic in the

centre. How should this be measured?
The longest diameter of the entire lesion should be followed. Eventually,

necrotic lesions which are responding to treatment decrease in size. In
reporting the results of trials, you may wish to report on this
phenomenon if it is seen frequently since some agents (e.g. angiogenesis
inhibitors) may produce this effect
If I am going to use MRI to follow disease, what is minimum size

for measurability?
MRI may be substituted for contrast enhanced CT for some sites, but not
lung. The minimum size for measurability is the same as for CT (10 mm)
as long as the scans are performed with slice thickness of 5 mm and no
gap. In the event the MRI is performed with thicker slices, the size of a
measurable lesion at baseline should be two times the slice thickness. In
the event there are inter-slice gaps, this also needs to be considered in
determining the size of measurable lesions at baseline
Can PETCT be used with RECIST?
At present, the low dose or attenuation correction CT portion of a

combined PETCT is not always of optimal diagnostic CT quality for use
with RECIST measurements. However, if your site has documented that
the CT performed as part of a PETCT is of the same diagnostic quality as
a diagnostic CT (with IV and oral contrast) then the PETCT can be used
for RECIST measurements. Note, however, that the PET portion of the CT
introduces additional data which may bias an investigator if it is not
routinely or serially performed
R E F E R E N C E S
1. Paesmans M, Sculier JP, Libert P, et al. Response to

chemotherapy has predictive value for further survival of
patients with advanced non-small cell lung cancer: 10 years
experience of the European Lung Cancer Working Party. Eur J
Cancer 1997;33:232632.
2. Buyse M, Thirion P, Carlson RW, et al. Relation between tumor
response to first-line chemotherapy and survival in advanced
colorectal cancer: a meta-analysis. Meta-analysis group in
Cancer. Lancet 2000;356:3738.
3. Goffin J, Baral S, Tu D, et al. Objective responses in patients
with malignant melanoma or renal cell cancer in early
clinical studies do not predict regulatory approval. Clin Cancer
Res 2005;15:592834.
4. El-Maraghi RH, Eisenhauer EA. Review of phase II trial designs
used in studies of molecular targeted agents: outcomes and
predictors of success in phase III. J Clin Oncol 2008;10:134654.
5. Miller AB, Hoogstraten B, Staquet M, Winkler A. Reporting
results of cancer treatment. Cancer 1981;47:20714.
6. Tonkin K, Tritchler D, Tannock I. Criteria of tumor response

used in clinical trials of chemotherapy. J Clin Oncol
1985;3:8705.
7. Baar J, Tannock I. Analyzing the same data in two ways: a
demonstration model to illustrate the reporting and
misreporting of clinical trials. J Clin Oncol 1989;7:96978.
8. Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines
to evaluate the response to treatment in solid tumors (RECIST
Guidelines). J Natl Cancer Inst 2000;92:20516.
9. Therasse P, Eisenhauer EA, Verweij J. RECIST revisited: a
review of validation studies on tumour assessment. Eur J
Cancer 2006;42:10319.
10. Bogaerts J, Ford R, Sargent D, et al. Individual patient
data analysis to assess modifications to the RECIST criteria.
Eur J Cancer 2009;45:24860.
11. Moskowitz CS, Jia X, Schwartz LH, Gonen M. A simulation
study to evaluate the impact of the number of lesions
measured on response assessment. Eur J Cancer
2009;45:30010.
12. Sargent D, Rubinstein L, Schwartz L, et al. Validation of novel
imaging methodologies for use as cancer clinical trials
end-points. Eur J Cancer 2009;45:2909.
13. Macdonald DR, Cascino TL, Schold Jr SC, Cairncross JG.

Response criteria for phase II studies of supratentorial
malignant glioma. J Clin Oncol 1990;8:127780.
14. Cheson BD, Pfistner B, Juweid ME, et al. Revised response
criteria for malignant lymphoma. J Clin Oncol 2007;10:57986.
15. Schwartz LH, Bogaerts J, Ford R, et al. Evaluation of lymph
nodes with RECIST 1.1. Eur J Cancer 2009;45:2617.
16. Rustin GJ, Quinn M, Thigpen T, et al. Re: New guidelines to
evaluate the response to treatment in solid tumors (ovarian
cancer). J Natl Cancer Inst 2004;96:4878.
17. Bubley GJ, Carducci M, Dahut W, et al. Eligibility and response
guidelines for phase II clinical trials in androgen-independent
prostate cancer: recommendations from the Prostate-Specific
Antigen Working Group. J Clin Oncol 1999;17:34617.
18. Scher H, Halabi S, Tannock I, et al. Design and end points of
clinical trials for patients with progressive prostate cancer
and castrate levels of testosterone: recommendations of the
Prostate Cancer Clinical Trials Working Group. J Clin Oncol
2008;26:114859.
19. Vergote I, Rustin GJ, Eisenhauer EA, et al. Re: new guidelines
to evaluate the response to treatment in solid tumors [ovarian
cancer]. Gynecologic Cancer Intergroup. J Natl Cancer Inst
2000;92:15345.
4 5 ( 2 0 0 9 ) 2 2 8 2 4 7
247
20. Van Glabbeke M, Verweij J, Judson I, Nielsen OS. EORTC Soft

Tissue and Bone Sarcoma Group: Progression-free rate as the
principal end-point for phase II trials in soft-tissue sarcomas.
Eur J Cancer 2002;38:5439.
21. Dancey JE, Dodd LE, Ford R, et al. Recommendations for the
assessment of progression in randomised cancer treatment
trials. Eur J Cancer 2009;45:2819.
22. Ford R, Schwartz L, Dancey J, et al. Lessons learned
from independent central review. Eur J Cancer 2009;45:
26874.
23. Catalano C, Francone M, Ascarelli A, Mangia M, Iacucci I,
Passariello R. Optimizing radiation dose and image quality.
Eur Radiol 2007;17(Suppl 6):F2632.
24. Low RN. Abdominal MRI advances in the detection of liver
tumours and characterization. Lancet Oncol 2007;8(6):52535.
25. Barrett T, Choyke PL, Kobayashi H. Imaging of the lymphatic
system: new horizons. Contrast Media Mol Imaging
2006;1(6):23045.
26. Shankar LK, Hoffman JM, Bacharach S, et al. National
Cancer Institute. Consensus recommendations for the use
of 18F-FDG PET as an indicator of therapeutic response
in patients in National Cancer Institute Trials.
J Nucl Med 2006;47(6):105966.

RECIST Guidelines

Uploaded by

Copyright:

Available Formats

RECIST Guidelines

Uploaded by

Document Information

Original Description:

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

RECIST Guidelines

Uploaded by

Copyright:

Available Formats

EUROPEAN JOURNAL OF CANCER

journal homepage: www.ejconline.com

New response evaluation criteria in solid tumours:

Background: Assessment of the change in tumour burden is an important feature of the

Received 17 October 2008

clinical evaluation of cancer therapeutics: both tumour shrinkage (objective response)

Accepted 29 October 2008

studies and literature reviews.

EUROPEAN JOURNAL OF CANCER

History of RECIST criteria

Assessment of the change in tumour burden is an important

to confusion in interpretation of trial results6 and in fact,

Why update RECIST?

Since RECIST was published in 2000, many investigators have

EUROPEAN JOURNAL OF CANCER

Process of RECIST 1.1 development

The RECIST Working Group, consisting of clinicians with

What about volumetric or functional assessment?

This raises the question, frequently posed, about whether it is

to such data emerging in the next few years to allow the

Purpose of this guideline

This guideline describes a standard approach to solid tumour

Measurability of tumour at baseline

At baseline, tumour lesions/lymph nodes will be categorised

Tumour lesions: Must be accurately measured in at least one

EUROPEAN JOURNAL OF CANCER

All other lesions, including small lesions (longest diameter

Special considerations regarding lesion measurability

Bone lesions, cystic lesions, and lesions previously treated

Lesions with prior local treatment:.

Specifications by methods of measurements

All measurements should be recorded in metric notation,

should be performed as close as possible to the treatment

The same method of assessment and the same technique

EUROPEAN JOURNAL OF CANCER

the upper normal limit, however, they must normalise for a

Tumour response evaluation

volved organs, but in addition should be those that lend

This section provides the definitions of the criteria used to

Evaluation of target lesions

Complete Response (CR): Disappearance of all target lesions.

EUROPEAN JOURNAL OF CANCER

Progressive Disease (PD): At least a 20% increase in the sum

4.3.2. Special notes on the assessment of target lesions

Target lesions that become too small to measure. While on

Evaluation of non-target lesions

4.3.4. Special notes on assessment of progression of nontarget disease

When the patient also has measurable disease. In this setting,

EUROPEAN JOURNAL OF CANCER

disease from localised to widespread, or may be described in

The appearance of new malignant lesions denotes disease

A positive FDG-PET scan lesion means one which is FDG avid

Evaluation of best overall response

The best overall response is the best response recorded from

Time point response

Missing assessments and inevaluable designation

When no imaging/measurement is done at all at a particular

Best overall response: all time points