Individual patient data analysis to assess modifications to the RECIST criteria

Published:December 17, 2008DOI:



      After the initial RECIST 1.0 were published in 2000, the criteria were widely implemented in the scientific oncology community. Since then, the RECIST working group has identified several issues to examine further. Two key issues that required careful, data-based assessment were the maximum number of lesions that should be assessed at each evaluation and the added value of requiring confirmation of response.


      To address these questions, data were obtained from 16 clinical trials in metastatic cancer, with patients enrolled between 1993 and 2005. A total of 6512 patients were included in the primary analysis dataset, accounting for over 18,000 potential target lesions. Nine percent of the included patients (n = 585) had six or more reported target lesions. The response and progression outcomes in the database were calculated using an adjusted RECIST methodology with a maximum of 5 (or 3) target lesions with/without confirmation and this was compared to the original RECIST version 1.0 which required up to 10 target lesions plus confirmation of response.


      Assessment of 5 lesions per patient led to a difference in best overall response assignment for an estimated 209 (3.2%) patients as compared to RECIST version 1.0. However, these changes did not affect the overall response rate. Progression-free survival was only minimally affected by measuring fewer lesions. In contrast, removing the requirement for response confirmation led to a significant increase in the numbers of patients classified as responders, resulting in a relative increase of approximately 19% in response rate. An algorithm using a maximum of three target lesions shows high concordance with the 10 lesions requirement in terms of response and TTP assignment. Concern that appropriate assessment of disease within an organ requires two lesions to be followed per organ suggests the approach of following two target lesions per organ, up to a maximum of five target lesions overall. Both strategies seem reasonable based on the data warehouse. The requirement of response confirmation in trials where this is a primary end-point is recommended to be maintained as its removal would substantially increase reported response rates.


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        • Therasse P.
        • Arbuck S.G.
        • Eisenhauer E.A.
        • et al.
        New guidelines to evaluate the response to treatment in solid tumors.
        J Natl Cancer Inst. 2000; 92
        • Bontenbal M.
        • Creemers G.-J.
        • Braun H.J.
        • et al.
        Phase II to III study comparing doxorubicin and docetaxel with fluorouracil, doxorubicin, and cyclophosphamide as first-line chemotherapy in patients with metastatic breast cancer: results of a Dutch Community Setting Trial for the Clinical Trial Group of the Comprehensive Cancer Centre.
        JCO. 2005; 23: 7081-7088
        • Giaccone G.
        • Herbst R.S.
        • Manegold C.
        • et al.
        Gefitinib in combination with gemcitabine and cisplatin in advanced non-small-cell lung cancer: a phase III trial—INTACT 1.
        JCO. 2004; 22: 777-784
        • Herbst R.S.
        • Giaccone G.
        • Schiller J.H.
        • et al.
        Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase III trial—INTACT 2.
        JCO. 2004; 22: 785-794
        • Jassem J.
        • Pien´kowski T.
        • Pluzanska A.
        • et al.
        • for the Central & Eastern Europe and Israel Paclitaxel Breast Cancer Study Group
        Doxorubicin and paclitaxel versus fluorouracil, doxorubicin, and cyclophosphamide as first-line therapy for women with metastatic breast cancer: final results of a Randomized Phase III Multicenter Trial.
        JCO. 2001; 19: 1707-1715
        • Chan S.
        • Friedrichs K.
        • Noel D.
        • et al.
        • for the 303 Study Group
        Prospective randomized trial of docetaxel versus doxorubicin in patients with metastatic breast cancer.
        JCO. 1999; 17: 2341-2354
        • Nabholtz J.M.
        • Falkson C.
        • Campos D.
        • et al.
        Docetaxel and doxorubicin compared with doxorubicin and cyclophosphamide as first-line chemotherapy for metastatic breast cancer: results of a Randomized, Multicenter, Phase III Trial.
        JCO. 2003; 21: 968-975
        • Mackey J.R.
        • Paterson A.
        • Dirix L.
        • et al.
        Final results of the phase III randomised trial comparing docetaxel (T), doxorubicin (A) and cyclophosphamide (C) to FAC as first line chemotherapy (CT) for patients (pts) with metastatic breast cancer (MBC).
        Proc Am Soc Clin Oncol. 2002; 21 ([abstr 137]): 35a
        • Hurwitz H.I.
        • Fehrenbacher L.
        • Hainsworth J.D.
        • et al.
        Bevacizumab in combination with fluorouracil and leucovorin: an active regimen for first-line metastatic colorectal cancer.
        JCO. 2005; 23: 3502-3508
        • Herbst R.S.
        • Prager D.
        • Hermann R.
        • et al.
        TRIBUTE: a phase III trial of erlotinib hydrochloride (OSI-774) combined with carboplatin and paclitaxel chemotherapy in advanced non-small-cell lung cancer.
        JCO. 2005; 23: 5892-5899
        • Paridaens R.
        • Biganzoli L.
        • Bruning P.
        • et al.
        Paclitaxel versus doxorubicin as first-line single-agent chemotherapy for metastatic breast cancer: a European Organization for Research and Treatment of Cancer Randomized Study with cross-over.
        J Clin Oncol. 2000; 18: 724-733
        • Biganzoli L.
        • Cufer T.
        • Bruning P.
        • et al.
        Doxorubicin and paclitaxel versus doxorubicin and cyclophosphamide as first-line chemotherapy in metastatic breast cancer: the European Organization for Research and Treatment of Cancer 10961 Multicenter Phase III Trial.
        JCO. 2002; 20: 3114-3121
        • Gatzemeier U.
        • Pluzanska A.
        • Szczesna A.
        • et al.
        Phase III Study of Erlotinib in combination with cisplatin and gemcitabine in advanced non-small-cell lung cancer: The Tarceva Lung Cancer Investigation Trial.
        JCO. 2007; 25: 1545-1552
        • Köhne C.H.
        • van Cutsem E.
        • Wils J.
        • et al.
        Phase III study of weekly high-dose infusional fluorouracil plus folinic acid with or without irinotecan in patients with metastatic colorectal cancer: European Organisation for Research and Treatment of Cancer Gastrointestinal Group Study 40986.
        JCO. 2005; 23: 4856-4865
        • Casali P.G.
        • Garrett C.R.
        • Blackstein M.E.
        • et al.
        Updated results from a phase III trial of sunitinib in GIST patients (pts) for whom imatinib (IM) therapy has failed due to resistance or intolerance.
        JCO. 2006; 24: 9513
      1. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumors: Revised RECIST guideline (version 1.1). Eur J Cancer, 2009;45:228–47.

        • Zacharia T.T.
        • Saini S.
        • Halpern E.F.
        • Sumner J.E.
        CT of colon cancer metastases to the liver using modified RECIST criteria: determining the ideal number of target lesions to measure AJR. 2006; 186
        • Schwartz L.H.
        • Mazumdar M.
        • Brown W.
        • Smith A.
        • Panicek D.M.
        Variability in response assessment in solid tumors: effect of number of lesions chosen for measurement.
        Clin Cancer Res. 2003; 9: 4318-4323
      2. Hillman SL, An M-W, O’Connell MJ, et al. An evaluation of the optimal number of lesions needed for tumor evaluation using the RECIST criteria: A North Central Cancer Treatment Group (NCCTG) Investigation, submitted for publication.

        • Ford R.
        • Schwartz L.
        • Dancey J.
        • et al.
        Lessons learned from independent central review.
        Eur J Cancer. 2009; 45: 268-274
        • Schwartz L.H.
        • Bogaerts J.
        • Ford R.
        • et al.
        Evaluation of lymph nodes with RECIST 1.1.
        Eur J Cancer. 2009; 45: 261-267
        • Ratain M.J.
        • Sargent D.J.
        Optimizing the design of phase II oncology trials: The importance of randomization.
        Eur J Cancer. 2009; 45: 275-280
        • Dancey J.E.
        • Dodd L.E.
        • Ford R.
        • et al.
        Recommendations for the assessment of progression in randomized cancer treatment trials.
        Eur J Cancer. 2009; 45: 281-289
        • Hopper K.D.
        • Kasales C.J.
        • Van Slyke M.A.
        Analysis of interobserver and intraobserver variability in CT tumor measurements.
        AJR. 1996; 167: 851-854
        • Preda L.
        • Lovati E.
        • Chiesa F.
        • et al.
        Measurement by multidetector CT scan of the volume of hypopharyngeal and laryngeal tumours: accuracy and reproducibility.
        Eur Radiol. 2007; 17: 2096-2102
        • Gietema H.A.
        • Schaefer-Prokop C.M.
        • Mali W.P.T.M.
        • et al.
        Pulmonary nodules: Interscan variability of semiautomated volume measurements with multisection CT – influence of inspiration level, nodule size and segmentation performance.
        Radiol. 2007; 245: 888-894
        • Erasmus J.J.
        • Gladish G.W.
        • Broemeling L.
        • et al.
        Interobserver and Intraobserver variability in measurement of non-small-cell carcinoma lung lesions: implications for assessment of tumor response.
        JCO. 2003; 21: 2574-2582
        • Punnen S.
        • Haider M.A.
        • Lockwood G.
        • Moulding F.
        • O’Malley M.E.
        • Jewett M.A.
        Variability in size measurement of renal masses smaller than 4 cm on computerized tomography.
        J Urol. 2006; 176: 2386-2390