Response Assessment Criteria for Clinical Trials Tumor Imaging Metrics Core January 29, 2008 Cheryl...

Response Assessment Criteria for Clinical TrialsTumor Imaging Metrics Core

January 29, 2008

Cheryl A. Sadow, MDAbdominal Imaging & Intervention DivisionBrigham & Women’s Hospital

Copyright © 2008 TIMC, Matthew A. Barish M.D. All rights reserved. 2

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


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


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


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)


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


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


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


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


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


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


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)


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


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)


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)


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


Tumor Response – New Lesions

• New Lesions = Progression (PD)

• Any new malignant lesion

• Any re-appearing lesion


Tumor Response - Summarized

Target LesionsNon-target

LesionsNew 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


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


Pleural Effusion & Ascites

Note:

New or enlarging pleural effusions or ascites evidenced radiographically will NOT be assumed to be malignant


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 Qualitative

Spleen/Liver

Biochemical

3 Pathological Bone Marrow Semi-quantitative


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


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 >1.5 cm LD that has regressed by >75 % in (unconfirmed) 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


Tumor Response - SummarizedResponse category

Physical Evaluation

Lymph Nodes

Lymph Node Masses Bone Marrow

CR Normal Normal Normal Normal

CRu Normal Normal Normal Indeterminate

Normal Normal >75% decrease

Normal or Indeterminate

PR Normal Normal Normal Positive

Normal >=50% decrease

>=50% decrease Irrelevant

Decrease in liver/spleen

>=50% decrease

>=50% decrease Irrelevant

Relapse/ Progression

Enlarging liver/spleen; new sites

New or Increased

New or Increased Reappearance


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


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


Thank you for your attention

Response Assessment Criteria for Clinical Trials Tumor Imaging Metrics Core January 29, 2008 Cheryl...

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