Response Evaluation Criteria in Solid Tumors

Response Evaluation Criteria In Solid Tumors(RECIST) is a set of published rules that dene whentumors in cancer patients improve (respond), stay thesame (stabilize), or worsen (progress) during treat-ment. The criteria were published in February 2000by an international collaboration including the EuropeanOrganisation for Research and Treatment of Cancer(EORTC), National Cancer Institute of the United States,and the National Cancer Institute of Canada Clinical Tri-als Group. Today, the majority of clinical trials evaluat-ing cancer treatments for objective response in solid tu-mors use RECIST.These criteria were developed and published in Febru-ary 2000, and subsequently updated in 2009. They arespecically NOT meant to determine whether patientshave improved or not, as these are tumor-centric, not pa-tient centric criteria. This distinction must be made byboth the treating physicians and the cancer patients them-selves. Many oncologists in their daily clinical practicefollow their patients malignant disease by means of re-peated imaging studies and make decisions about contin-uing therapy on the basis of both objective and symp-tomatic criteria. It is not intended that these RECISTguidelines play a role in that decision making, except ifdetermined appropriate by the treating oncologist.

1 Eligibility Only patients with measurable disease at baselineshould be included in protocols where objective tu-mor response is the primary endpoint.

Measurable disease - the presence of at least one measur-able lesion. If the measurable disease is restricted to asolitary lesion, its neoplastic nature should be conrmedby cytology/histology.Measurable lesions - lesions that can be accurately mea-sured in at least one dimension with longest diameter 20mm using conventional techniques or 10 mm by spiralCT scan.Non-measurable lesions - all other lesions, includingsmall lesions (longest diameter

2 5 CONFIRMATION

Therefore, the utilization of such techniques for ob-jective tumor response should be restricted to val-idation purposes in specialized centers. However,such techniques can be useful in conrming com-plete pathological response when biopsies are ob-tained.

Tumor markers alone cannot be used to assess re-sponse. If markers are initially above the upper nor-mal limit, they must normalize for a patient to beconsidered in complete clinical response when all le-sions have disappeared.

Cytology and histology can be used to dierenti-ate between PR and CR in rare cases (e.g., aftertreatment to dierentiate between residual benignlesions and residual malignant lesions in tumor typessuch as germ cell tumors).

3 Baseline documentation of Tar-get and Non-Target lesions

All measurable lesions up to a maximum of 2 lesionsper organ and 5 lesions in total, representative of allinvolved organs should be identied as target lesionsand recorded and measured at baseline.

Target lesions should be selected on the basis of theirsize (lesions with the longest diameter) and theirsuitability for accurate repeated measurements (ei-ther by imaging techniques or clinically).

A sum of the longest diameter (LD) for all target le-sions will be calculated and reported as the baselinesum LD. The baseline sum LD will be used as ref-erence by which to characterize the objective tumorresponse.

All other lesions (or sites of disease) should beidentied as non-target lesions and should also berecorded at baseline. Measurements of these lesionsare not required, but the presence or absence of eachshould be noted throughout follow-up.

4 Response CriteriaEvaluation of target lesions

Complete Response (CR): Disappearance of all targetlesions

Partial Response (PR): At least a 30% decrease in thesum of the LD of target lesions, taking as referencethe baseline sum LD

Stable Disease (SD): Neither sucient shrinkage toqualify for PR nor sucient increase to qualify forPD, taking as reference the smallest sum LD sincethe treatment started

Progressive Disease (PD): At least a 20% increase inthe sum of the LD of target lesions, taking as refer-ence the smallest sum LD recorded since the treat-ment started or the appearance of one or more newlesions

Evaluation of non-target lesions

Complete Response (CR): Disappearance of all non-target lesions and normalization of tumor markerlevel

Incomplete Response/ Stable Disease (SD): Persis-tence of one or more non-target lesion(s) or/andmaintenance of tumor marker level above the nor-mal limits

Progressive Disease (PD): Appearance of one ormore new lesions and/or unequivocal progression ofexisting non-target lesions

Evaluation of best overall responseThe best overall response is the best response recordedfrom the start of the treatment until disease progres-sion/recurrence (taking as reference for PD the smallestmeasurements recorded since the treatment started). Ingeneral, the patients best response assignment will de-pend on the achievement of both measurement and con-rmation criteria

Patients with a global deterioration of health statusrequiring discontinuation of treatment without ob-jective evidence of disease progression at that timeshould be classied as having symptomatic deteri-oration. Every eort should be made to documentthe objective progression even after discontinuationof treatment.

In some circumstances it may be dicult to distin-guish residual disease from normal tissue. When theevaluation of complete response depends on this de-termination, it is recommended that the residual le-sion be investigated (ne needle aspirate/biopsy) toconrm the complete response status.

5 Conrmation The main goal of conrmation of objective responseis to avoid overestimating the response rate ob-served. In cases where conrmation of response isnot feasible, it should be made clear when reportingthe outcome of such studies that the responses arenot conrmed.

3 To be assigned a status of PR or CR, changes in tu-mor measurements must be conrmed by repeat as-sessments that should be performed no less than 4weeks after the criteria for response are rst met.Longer intervals as determined by the study proto-col may also be appropriate.

In the case of SD, follow-up measurements musthave met the SD criteria at least once after study en-try at a minimum interval (in general, not less than6-8 weeks) that is dened in the study protocol

Duration of overall response

The duration of overall response is measured fromthe time measurement criteria are met for CR or PR(whichever status is recorded rst) until the rst datethat recurrence or PD is objectively documented,taking as reference for PD the smallest measure-ments recorded since the treatment started.

6 Duration of stable disease SD is measured from the start of the treatment untilthe criteria for disease progression are met, taking asreference the smallest measurements recorded sincethe treatment started.

The clinical relevance of the duration of SD variesfor dierent tumor types and grades. Therefore, itis highly recommended that the protocol specify theminimal time interval required between two mea-surements for determination of SD. This time in-terval should take into account the expected clinicalbenet that such a status may bring to the populationunder study.

Response review

For trials where the response rate is the primary end-point it is strongly recommended that all responsesbe reviewed by an expert(s) independent of the studyat the studys completion. Simultaneous review ofthe patients les and radiological images is the bestapproach.

Reporting of results

All patients included in the study must be assessedfor response to treatment, even if there are majorprotocol treatment deviations or if they are ineligi-ble. Each patient will be assigned one of the follow-ing categories: 1) complete response, 2) partial re-sponse, 3) stable disease, 4) progressive disease, 5)early death from malignant disease, 6) early deathfrom toxicity, 7) early death because of other cause,or 9) unknown (not assessable, insucient data).

All of the patients who met the eligibility crite-ria should be included in the main analysis of theresponse rate. Patients in response categories 4-9should be considered as failing to respond to treat-ment (disease progression). Thus, an incorrect treat-ment schedule or drug administration does not resultin exclusion from the analysis of the response rate.Precise denitions for categories 4-9 will be proto-col specic.

All conclusions should be based on all eligible pa-tients.

Subanalyses may then be performed on the basis of asubset of patients, excluding those for whom majorprotocol deviations have been identied (e.g., earlydeath due to other reasons, early discontinuation oftreatment, major protocol violations, etc.). How-ever, these subanalyses may not serve as the basisfor drawing conclusions concerning treatment e-cacy, and the reasons for excluding patients from theanalysis should be clearly reported.

The 95% condence intervals should be provided.

7 See also Surveillance, Epidemiology, and End Resultsdatabase (SEER)

8 Citation RECIST article published in JNCI Guidelines and information from European Organi-zation for Research and Treatment in Cancer

Eur J Cancer. 2009 Jan;45(2):228-47. doi:10.1016/j.ejca.2008.10.026.

New response evaluation criteria in solid tumours: re-vised RECIST guideline (version 1.1).Guidelines (ver-sion 1.1)

Full presentation of newer guideline (14.7MB; .pdf)

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Eligibility Methods of Measurement Baseline documentation of Target and Non-Target lesions Response Criteria Confirmation Duration of stable disease See alsoCitation Text and image sources, contributors, and licensesTextImagesContent license