Response Assessment
Criteria for Clinical Trials
Tumor Imaging Metrics Core
January 29, 2008
Cheryl A. Sadow, MD
Abdominal Imaging & Intervention Division
Brigham & Women’s Hospital
RECIST
• Response Evaluation Criteria in Solid Tumors
•
Standardized repeatable method for measuring
response to therapy for solid tumors
•
NOT EQUIVALENT TO A CLINICAL READ!!!
• RECIST is a combination of both qualitative and
quantitative assessment
• Based on concept of target lesions and non-target lesions
•
Target lesions are quantitatively assessed
•
Non-target lesions are qualitatively assessed
Copyright © 2008 TIMC, Matthew A. Barish M.D. All rights reserved.
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RECIST
• Based on concept of target lesions and non-target lesions
•
Target lesions are chosen based on 3 factors:
• Must be EASILY (and reproducibly) measurable
• Must be representative of the disease (clearly metastasis)
• Must be representative of distribution (choose measurable lesions
from all involved organs)
• Non-target lesions are all other presumed manifestations
of the disease
•
All non-measurable lesions
•
Measurable lesions that were not chosen as target lesions
•
Lesions that may be (but not definitely) metastases
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Target Lesions
Target lesions must be measurable
Definition of Measurable Lesions
• Size Matters
• Conventional CT or MRI (non-spiral):
• If slice collimation <10mm, minimum lesion size is 20 mm
• If slice collimation >10mm, minimum lesion size is 2 x collimation
ex. Slice collimation = 15mm, minimum lesion size = 30mm
• Spiral CT
• If slice collimation <5mm, minimum lesion size is 10 mm
• If slice collimation >5mm, minimum lesion size is 2 x collimation
ex. Slice collimation = 7mm, minimum lesion size = 14mm
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Target Lesions
Target lesions must be reproducibly measurable
Definition of reproducibly measurable lesions
• Consistency across time points
• Pick lesions with well defined edges or margins
• Always measure longest diameter
• Measure lesions on same phase or same sequence (MRI)
• Only measure lesions that are definitely metastases
(If unsure don’t measure)
• Pick lesions that are stable in position, try to avoid mobile lesions
(Avoid mesenteric masses that change in position)
Copyright © 2008 TIMC, Matthew A. Barish M.D. All rights reserved.
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Target Lesions
Target lesions should represent distribution of disease
Definition of measurable lesions
• Representative of disease throughout body
• Pick lesions from disparate areas of the body
• Do not choose > 5 lesions in any one organ or anatomic location
• Organs are well defined
• Anatomic regions are up to individual interpretation (use best
judgment)
• For lymphoma choose nodes from different nodal stations
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Target Lesions
• Measurable lesions up to a maximum of
• 5 lesions per organ
• 10 lesions total
• Select based on size and reliability of measurement
• Sum of longest diameter (SLD) for all target lesions will be
calculated at baseline and used as reference to
characterize objective tumor response
Copyright © 2008 TIMC, Matthew A. Barish M.D. All rights reserved.
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Quantitative Assessment
• The “SLD” is the quantitative assessment
• SLD = sum of the longest diameters of target lesions
• This part of the evaluation is not subject to interpretation
• Strict rules and definitions of:
• Complete response = No measurable disease
• Partial Response = Greater than 30% decrease in score
• Stable Disease = Between 30% decrease and 20% increase
• Progression = Greater than 20% increase in score
Copyright © 2008 TIMC, Matthew A. Barish M.D. All rights reserved.
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Non – Target Lesions
• All aspects of disease not chosen as Target Lesions
• All non-measurable lesions
• Measurable lesions that were not chosen as target lesions
• Lesions that may be (but not definitely) metastases
• Non- measurable lesions
Not suitable for accurate repeated measurements
• Ascites
• Leptomeningeal disease
• Pleural effusions
• Inflammatory breast disease
• Cystic lesions
• Lymphangitis cutis/pulmonis
• Bone lesions
• Brain lesions
• Irradiated lesions
• Ground glass lung lesions
Copyright © 2008 TIMC, Matthew A. Barish M.D. All rights reserved.
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Measuring Lesions
• Baseline Scan – Initial Review
• Determine if a single measurable lesion is present
• Once single lesion is found, no need to evaluate any further
• Baseline scan – Full Review
• Determine target lesions and non-target lesions
• Target lesions
• Record site and longest diameter
• Measure longest diameter (LD) on slice where the lesion is largest
• Use magnification and appropriate window/level
• Non-target lesions
• Record site and description
• Will be assessed qualitatively in the future
Copyright © 2008 TIMC, Matthew A. Barish M.D. All rights reserved.
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Follow-up: Target Lesions
• On follow-up scans, once a lesion is identified as Target:
• Must continue to measure even if LD falls below size criteria
• Measure LD regardless of location (slice) or orientation on prior
scan
• Choose slice where lesion is largest, even if different than baseline
• Measure LD regardless of poor image quality or poorly defined
lesion boundaries (i.e., if target lesion is imaged, LD must be
measured)
• If a target lesion is visible but too small to measure, list as “5mm”
• If lesion is not imaged, enter “Unknown” (outside FOV)
If “unknown” is entered, comments are required
Copyright © 2008 TIMC, Matthew A. Barish M.D. All rights reserved.
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Follow-up Scans
• Target lesions on follow-up:
• If a lesion separates to form discrete lesions, measure LD of each
lesion and report separately (e.g. #3 -> 3 and 3a)
• If target lesion becomes confluent, measure LD of lesion and
record under 1 of the lesions and enter “0 mm” for other lesion(s)
• Non-target lesions on follow-up:
• All lesion region or organ that were selected will be followed and
their status will be recorded as:
• Absent: If totally resolved (CR)
• Unchanged, Improved, or ? increased but not clearly increased (SD)
• Clearly worse: Indicative of progression (PD)
• Not assessed: Missing, incomplete imaging (UN)
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Follow-up Scans
• New lesions seen on follow-up:
• Any lesion that appears after baseline (including new lesions in
irradiated areas)
• Any lesions that re-appear will be considered new lesions
• Lesions should be greater than the slice thickness (usually at least
6 mm) to be considered a new lesion
Copyright © 2008 TIMC, Matthew A. Barish M.D. All rights reserved.
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Measuring Lesions
• Liver lesions:
• Include the hypervascular peripheral component
• Measure in portal venous phase on CT
• Measured in post contrast T1 axial images (portal phase)
Copyright © 2008 TIMC, Matthew A. Barish M.D. All rights reserved.
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Tumor Response - Target Lesions
•
Complete response (CR): Disappearance of all target lesions
•
Partial response (PR): > 30% decrease in the SLD taking as reference
the baseline SLD
•
Stable decrease (SD): Neither sufficient shrinkage to qualify for PR nor
sufficient increase to qualify for PD
•
Progression (PD): > 20% increase in the SLD taking as reference the
nadir beginning with baseline measurement (if unknown is present then
that SLD cannot be used as reference)
•
Unknown (UN): If one or more unknown is present and the SLD is not
indicative of PD (explanatory comments required)
Copyright © 2008 TIMC, Matthew A. Barish M.D. All rights reserved.
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Tumor Response – Non-Target Lesions
•
Complete Response (CR): Disappearance of all non-target lesions
•
Incomplete Response/Stable Disease (SD): If one or more is
Unchanged or Improved and no PD, “not assessed” or “not done”
•
Progression (PD): If at least one “Clearly worse” is present
•
Unknown (UN): If “not assessed” or “not imaged” is present
Copyright © 2008 TIMC, Matthew A. Barish M.D. All rights reserved.
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Tumor Response – New Lesions
• New Lesions = Progression (PD)
•
Any new malignant lesion
•
Any re-appearing lesion
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Tumor Response - Summarized
Target Lesions
Non-target
Lesions
New Lesions
Overall
Response
CR
CR
No
CR
CR
SD
No
PR
PR
CR or SD
No
PR
SD
CR or SD
No
SD
PD
Any
Yes or No
PD
Any
PD
Yes or No
PD
Any
Any
Yes (PD)
PD
Copyright © 2008 TIMC, Matthew A. Barish M.D. All rights reserved.
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Surgery & Radiotherapy
Note:
If at all possible, lesions in areas of known radiation or
surgery should not be selected as target or non-target
lesions
Copyright © 2008 TIMC, Matthew A. Barish M.D. All rights reserved.
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Pleural Effusion & Ascites
Note:
New or enlarging pleural effusions or ascites
evidenced radiographically will NOT be assumed to
be malignant
Copyright © 2008 TIMC, Matthew A. Barish M.D. All rights reserved.
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Cheson Criteria
• Based on International Working Group Recommendations
• Standardized repeatable method for measuring response to
therapy for NHL
• Response is assessed on 3 criteria:
1
Radiological
Lymph nodes/
Quantitative
masses
2
Clinical
Physical Exam
Spleen/Liver
Biochemical
3
Pathological
Bone Marrow
Qualitative
Semi-quantitative
Copyright © 2008 TIMC, Matthew A. Barish M.D. All rights reserved.
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Node Selection
• Must be representative of the distribution of the disease
• Must be clearly and reproducibly measurable in at least 2
perpendicular dimensions
• Definition of Target Lesions
• Abnormal lymph nodes and/or nodal masses and/or hepatic/splenic
nodules (up to 6)
• >1.5 cm longest diameter and >1.0 cm transverse diameter
• Mediastinal and retroperitoneal areas of disease should be included
whenever these sites are involved
• Definition of Non-target Lesions
• Except for splenic or hepatic nodules, involvement of other organs is
considered non-measurable disease
• Any lymph nodes or nodal masses not selected as target lesions
Copyright © 2008 TIMC, Matthew A. Barish M.D. All rights reserved.
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Tumor Assessment – Response Criteria
• Radiological Criteria = Lymph Nodes / Masses
CR
<= 1.5 cm LD if >1.5 cm at baseline, or
<= 1 cm LD if between 1.1 to 1.5 cm, or
>75% decrease in SPD at baseline
CRu
(unconfirmed)
>1.5 cm LD that has regressed by >75 % in
SPD at baseline
PR
>= 50% decrease in SPD at baseline of 6
largest dominant nodes or nodal masses
No increases in other nodes
PD
>= 50% increase in SPD from nadir and/or
appearance of any new lesion
SD
Less than PR but not progression
Copyright © 2008 TIMC, Matthew A. Barish M.D. All rights reserved.
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Tumor Response - Summarized
Response
category
Physical
Evaluation
Node
Lymph Nodes Lymph
Masses
Bone Marrow
CR
Normal
Normal
Normal
Normal
CRu
Normal
Normal
Normal
Indeterminate
Normal
Normal
>75%
decrease
Normal or
Indeterminate
Normal
Normal
Normal
Positive
Normal
>=50%
decrease
>=50%
decrease
Irrelevant
Decrease in
liver/spleen
>=50%
decrease
>=50%
decrease
Irrelevant
Enlarging
liver/spleen;
new sites
New or
Increased
New or
Increased
Reappearance
PR
Relapse/
Progression
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Reviewer Selection Criteria Per ICH
Guidelines
• Chosen according to ICH Guidelines & other regulation
• Reviewers MUST have
• No financial interest in the outcome of the study
• No involvement in study design and conduct
• Agreed to no use of information learned during the course of the
trial without approval by sponsor
• M.D. with appropriate medical expertise in clinical area
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Data Form Requirements
• Reviewer is responsible for accuracy of data entered on
the form
• Upon completion, reviewer must sign the form
• Any changes necessary (once the CRF is signed) will be
considered a re-review
• All changes must be initialed and dated
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Thank you for your attention
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