New Response Evaluation Criteria for Lymphoma Clinical Trials: RECIL 2017


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New criteria for evaluating response in lymphoma clinical trials—RECIL 2017—have been developed by an International Working Group with the aim of harmonizing criteria with the RECIST criteria used for solid tumors.1 The new criteria were reported by Anas Younes, MD, of Memorial Sloan Kettering Cancer Center, and colleagues in Annals of Oncology.

The standard response criteria for lymphoma are the Lugano Classification, based on [18F]2-fluoro-2-deoxy-D-glucose positron-emission tomography (FDG-PET) or bidimensional tumor measurements on computed tomography (CT) scans. The Response Evaluation Criteria in Solid Tumors (RECIST) are based on single-dimensional measurements.


Future directions should evaluate the role of molecular depth of response in predicting treatment outcome and to guide future studies aimed at evaluating shorter duration of therapy.
— Anas Younes, MD, and Colleagues

A group of international lymphoma experts from academic centers and pharmaceutical companies, radiologists, and statisticians collaborated to harmonize lymphoma response criteria with RECIST, hypothesizing that single-dimension measurement could be used to assess response, with results similar to those with standard criteria. The hypothesis was tested by analysis of 47,828 imaging measurements from 2,983 adult and pediatric lymphoma patients from 10 multicenter clinical trials. The resultant RECIL criteria were introduced at the International Workshop on Non-Hodgkin Lymphoma (San Diego 2016). The investigators found that assessment of tumor burden in lymphoma clinical trials can be performed using the sum of longest diameters of a maximum of three target lesions and that a novel provisional category of minor response warranted inclusion.

Elements of the RECIL response criteria are reproduced here.

Assessment of Tumor Burden

Assessment of tumor burden in lymphoma clinical trials can use the sum of longest diameters. In patients with disseminated disease, a maximum of three target lesions should be selected and used to estimate tumor response. Target lesions should be selected from those with the largest size that can be reproducibly measured and should preferably represent multiple sites or organs. In most cases, lymph nodes can be considered target lesions if the lymph node longest diameter is ≥ 15 mm.

Response Categories
Complete Response 

  • Complete disappearance of all target lesions and all nodes with long axis < 10 mm
  • ≥ 30% decrease in the sum of longest diameters of target lesions (partial response) plus normalization of FDG-PET
  • Normalization of FDG-PET (Deauville score 1 to 3)
  • No bone marrow involvement
  • No new lesions
  • Reduction in the sum of diameters by ≤ 30% with normalization of FDG-PET uptake should not be considered a complete response unless documented by negative tissue biopsy.

Partial Response

  • ≥ 30% decrease in the sum of longest diameters of target lesions but not a complete response
  • Positive FDG-PET (Deauville score 4 to 5)
  • Any bone marrow involvement
  • No new lesions

Minor Response

  • ≥ 10% decrease in the sum of longest diameters of target lesions but not a partial response
  • Any FDG-PET finding
  • Any bone marrow involvement
  • No new lesions

Stable Disease

  • < 10% decrease or ≤ 20% decrease in the sum of longest diameters of target lesions
  • Any FDG-PET finding
  • Any bone marrow involvement
  • No new lesions

Progressive Disease

  • > 20% increase in the sum of longest diameter of target lesions
  • For small lymph nodes of < 15 mm posttherapy, minimum absolute increase of 5 mm and long diameter > 15 mm
  • Appearance of new lesion
  • Any FDG-PET finding
  • Any bone marrow involvement
  • New or no new lesions

Disease Progression After Initial Response

After initial response, and in the absence of appearance of new lesions, progressive disease is defined as an increase of the nadir sum of diameters by > 20%.

Response Assessment to Immune-Modulating Agents, Including Checkpoint Inhibitors

To account for potential “pseudo-progression,” immune--related response criteria should be used, requiring confirmation of progressive disease on two consecutive scans at least 4 weeks apart and inclusion of new lesion measurements in the total tumor burden. If serial imaging confirms the prior increase in tumor measurements was related to an early manifestation of disease progression rather than tumor flare, the time of disease progression should be backdated to the initial scans that documented progressive disease.

Appearance of New Extranodal Lesion

A minimum of 1 cm in largest diameter of new extranodal lesions is required to confirm progressive disease. New smaller but suspicious lesions should be designated as equivocal; if later they are confirmed (by CT or biopsy) as due to lymphoma, the documented date of disease progression should be the date of identification as equivocal.

Disseminated Disease

The status of nontarget lesions should be taken into account before formulating the final response status. The International Working Group statement provides a recommended approach to response designation involving best response of target and nontarget lesions.

Frequency of Response Assessment

In phase I/II clinical trials in previously treated patients, response should be assessed every 2 to 3 months during the first year of therapy. In the absence of new symptoms or clinical concerns, subsequent imaging studies can be performed every 3 or 4 months during the second year and every 6 months thereafter, for the duration specified in the clinical trial. Imaging assessment may be carried out less frequently during and after therapy for newly diagnosed patients and in the setting of randomized phase III studies.

BASIS OF RECIL 2017

  • 47,828 imaging measurements
  • Data from 2,983 adult and pediatric patients with lymphoma
  • 10 multicenter clinical trials represented

The authors concluded: “Future directions should evaluate the role of molecular depth of response (minimal residual disease and circulating DNA) in predicting treatment outcome and to guide future studies aimed at evaluating shorter duration of therapy. Our new RECIL proposal should also be evaluated by the RECIST investigators to consider further harmonization of the criteria, with a special attention to the measurement of the long axis of lymph nodes, optimal number of target lesions, and introduction of [minor response] category.” ■

DISCLOSURE: For full disclosures of the study authors, visit www.annsurgoncol.org.

REFERENCE

1. Younes A, Hilden P, Coiffier B, et al: International Working Group consensus response evaluation criteria in lymphoma (RECIL 2017). Ann Oncol 28:1436-1447, 2017.



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