1. RECIST Overview

2. Introduction What is RECIST? RECIST Endpoints in Berenice Definitions
Methods of Assessment
Schedule of Assessments
Evaluation of Tumour Response
Minimum Source Data Requirements
Summary

3. Response Evaluation Criteria In Solid Tumours
What is RECIST?
Response Evaluation Criteria In Solid Tumours
A set of published rules that define when cancers improve (respond), stay the same (stable) or worsen (progress) during treatment
Standardises solid tumor response evaluation => uniform reporting of clinical study outcomes
Response Evaluation Criteria in SolidTumors (RECIST) Version 1.1 (Eisenhauer et al. 2009).

4. Berenice RECIST Efficacy Outcome Measures
Clinical response, defined as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) prior to surgery.
The clinical response rate is defined as the proportion of patients in the ITT population who achieve a CR or PR prior to surgery.
Tumor response will be assessed prior to each new cycle of therapy by clinical examination and/or, mammography, and/or other methods of evaluation as per local practice.
Response will be assessed by the investigator as per local practice based on the principles of Response Evaluation Criteria in SolidTumors (RECIST) Version 1.1 (Eisenhauer et al. 2009).
The RECIST eCRF pages in Berenice are for collection of RECIST outcomes in the NEOADJUVANT period only

5. Definitions – Target Lesions
Selected at baseline
All measurable lesions
Minimum of 1 maximum of 10
No more than 5 per organ
Representative of all involved organs
Selected based on size and suitability for accurate repeated measurements
Unidimensional measurements (longest diameter) required for each target lesion at all assessed time points.

6. Definitions – Non Target Lesions
Selected at baseline
All other lesions that are not selected at baseline
Excess measurable lesions ( e.g. when 10 have already been identified as target lesions)
All non-measurable lesions
Measurements are not required

7. Definitions – Non Measurable Lesions
All other lesions including
Small lesions < 20mm with conventional techniques of <10mmwith spiral CT
Bone lesions
Previously irradiated lesions
Ascites, pleural effusions, cystic lesions etc.

8. Definitions – New Lesions
Any lesion present on a follow up tumour assessment that was not present at baseline
NTL = New Target Lesion

9. Methods of Assessment Target Lesions
Non- Target Lesions and New Lesions
Recommended
CT (preferred)
MRI
Accepted
Clinical Examination
Chest X Ray
Mammogram
Ultrasound
X Ray
Endoscopy

10. Methods of Assessment
Important to use the same imaging/examination methods to follow lesions
Baseline method must be followed as much as is practical throughout the trial
Bone scan, PET scan, angiography, tumor markers and cytology/histopathology are not acceptable methods as part of the RECIST framework

11. Schedule of Assessments
Baseline Tumour Assessments
Follow Up Assessments
Unscheduled Tumor Assessments
Clinical tumor assessment will be performed as per local medical practice based on the principles of RECIST version 1.1 criteria. During the
adjuvant treatment period, patients should be assessed for recurrence at least every 3 months (Cycle 9, Cycle 13, Cycle 17, and Cycle 21), and
at the study completion or early termination visit.

12. Evaluation of Response
Complete Response (CR)
All target lesions have disappeared completely (diameters =0)
Partial Response (PR)
Sum of the long diameters (LD) of the target lesions have shrunk by >/= 30% compared to the sum of long diameters at baseline
Progressive Disease (PD)
Sum of the LD for the target lesions have grown by >/= 20% compared to the smallest sum of the previously recorded LD
Note: not necessarily baseline
Stable Disease (SD)
Neither sufficient shrinkage for PR or growth for PD
i.e. conditions of PD, CR and PR are not satisfied
Not Evaluable (NE)
Any missing target lesion data
As assessed by investigator

13. New Lesion Visit Response
The presence or absence of new lesions must be recorded at each tumor assessment visit
Detection of a new lesion = progressive disease (PD)
If in doubt, confirm the presence before recording on eCRF

18. Overall Visit Response
Combination of TL response, NTL response and presence, absence of new lesions
RECIST overall response categories
If patient has PD of TL, NTL or an appearance of a new lesion, the overall response will be a PD ( PD always overrides)
If TL or NTL assesment is NE, then the overall assessment will also be NE unless there is clear evidence of progression e.g. a new lesion.

19. Confirmation of Response
A responder is defined as a patient who has a confirmed CR or PR
What do we mean by confirmed?
Initial overall visit response of CR or PR
Confirmation of response ( overall visit repsnise of CR or PR) at the next scheduled tumor assessment visit ( no less than 4 weeks later)
Why do we confirm responses?
to avoid overestimating the response rate observed.

20. Minimum Source Data Requirements
Target Lesions and Non Target Lesions at baseline and follow up
Site and location
Date of assessment and method used
Any lesion interventions (e.g. irradiation/surgery)
Longest diameter measurements ( target lesions only)
Reasons for any missing or non evlauable assessments
Reasons for any inconsistencies between radiology report and patient notes
Details of any new lesions ( site, location, date of assessment and method used)
Overall assessment of non target lesion response (RECIST response as calculated by investigator)
Investigator’s opinion of response

21. Summary RECIST is used to standardise tumour response evaluation
Baseline documentation of tumour burden in terms of Target and Non – Target Lesions
Target lesions are selected on the basis of their size and suitability for accurate repeated measurements
Tumour assessments must be performed in accordance with visit schedule to avoid bias
All patients must be followed for progression even if
Discontinued randomised treatments
Started another anticancer treatment

22. Doing now what patients need next