Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Aug 10;38(23):2667-2676.
doi: 10.1200/JCO.19.02985. Epub 2020 Jun 18.

Response Criteria for Intratumoral Immunotherapy in Solid Tumors: itRECIST

Gregory V Goldmacher  1 , Anuradha D Khilnani  1 , Robert H I Andtbacka  2 , Jason J Luke  3 , F Stephen Hodi  4 , Aurelien Marabelle  5 , Kevin Harrington  6 , Andrea Perrone  1 , Archie Tse  7 , David C Madoff  8 , Lawrence H Schwartz  9
Affiliations
Review

Response Criteria for Intratumoral Immunotherapy in Solid Tumors: itRECIST

Gregory V Goldmacher et al. J Clin Oncol. .
No abstract available

PubMed Disclaimer

Figures

FIG 1.
FIG 1.
Algorithm for classification of lesions into 4 categories at baseline and recategorization after baseline. (A) Classification of lesions at baseline. Lesions are classified first as measurable or nonmeasurable using the standard RECIST 1.1 rules for measurability. Measurable lesions (those eligible for selection as target lesions) are then classified as target (selected to be observed quantitatively) or nontarget (selected to be observed qualitatively), and the decisions about which lesions are to be injected are made based on the prioritization rules discussed. Lesions selected for injection may be either target or nontarget in RECIST 1.1 terms. Between 1 and 5 lesions should be classified as target injected (T-I), and between 1 and 5 should be classified as target noninjected (T-NI), for a maximum of 10 target lesions. All lesions not chosen as target are observed qualitatively as nontarget, and some of these may be selected for injection at baseline. T-I lesions and T-NI lesions each have their own distinct sum of diameters (SOD; longest diameters for extranodal lesions, short axis for lymph nodes). A combined SOD also includes all target lesions, injected and noninjected. Nontarget injected (NT-I) and nontarget noninjected (NT-NI) lesions are observed qualitatively, exactly as in RECIST 1.1, classified in aggregate as showing complete response (CR), unequivocal progressive disease (PD), or neither (called non-CR/non-PD in RECIST 1.1). (B) T-NI or NT-NI lesions can be recategorized as injected lesions if the decision is made to inject them after baseline assessment. NT-NI lesions may be injected if previously injected nontarget lesions regress completely or become inaccessible, or if a patient factor such as injection-site reaction or patient intolerance precludes further injection. Lesions initially selected as T-NI should remain noninjected for as long as possible so that the maximal noninjected effect can be evaluated, but they may be injected if they are enlarging or if no other lesions are available for injection, especially if the lesions initially designated as T-NI are not regressing. The barrier between target and nontarget categories means that all lesions remain target and nontarget in accordance with the initial designation, regardless of whether they are subsequently injected.
FIG 2.
FIG 2.
Overall response until disease progression per RECIST 1.1. The injected response at each visit is based only on the changes in the sum of diameters (SOD) of the lesions designated as target injected (T-I). The noninjected response at each visit is based only on the changes in the SOD of the target noninjected (T-NI) lesions. The overall response is based on the changes in the SOD of all target lesions together, the qualitative assessment of all nontarget lesions together, and the evaluation for possible new lesions and uses the same response categories and logical combination of these that RECIST 1.1 uses. NT-I, nontarget injected; NT-NI, nontarget noninjected.
FIG 3.
FIG 3.
Example of iterative assessment of injected lesion response during treatment. This is an illustration of overall, injected, and noninjected response assessment, with a particular focus on the iterative assessment of injected lesions. All lesions from a single patient are displayed in simple schematic form and are not meant to be anatomically adjacent. For purposes of this illustration, the yellow and green lesions were selected at baseline as target injected (T-I), and the purple and blue lesions were selected as target noninjected (T-NI); there are no nontarget lesions. In this simplified example, a full imaging assessment is performed at each treatment visit just before the decision about which lesions to inject at that visit. The overall response at each visit was based on the change in sum of diameters (SOD) for all the target lesions together (because there are no nontarget lesions in this example). Once progressive disease (PD) is observed (in this case, because of a new lesion), the overall response assessment thereafter is similar to that of RECIST for immunotherapeutic trials (iRECIST). The injected response is based on the change in SOD of the injected lesions from the assessment immediately before this one. The noninjected response is based on the changes in SOD from baseline and nadir and is considered nonevaluable (NE) once any lesion that was initially selected as T-NI is subsequently injected, as happens in this case with the blue lesion. If this lesion were to grow later, it could contribute to an overall response of PD. iPR, immunotherapeutic partial response; PR, partial response; SD, stable disease.
FIG 4.
FIG 4.
Management algorithm at initial radiographic progression (A) without and (B) with new lesions. (A) If initial radiographic progression does not involve new lesions, management depends first on whether the patient is clinically stable. If the patient has not experienced clinical decline and the physician and patient decide to continue treatment, the lesions that are enlarging (if they are accessible and can be safely injected) should be injected. Lesions that were previously classified as noninjected may be reclassified as injected at this time, although the target and nontarget categories must be strictly preserved. (B) If progression involves new lesions that are accessible and can be safely injected, they should be prioritized for injection. New lesions that are measurable can contribute to a new lesion sum of diameters for an overall response assessment that resembles RECIST for immunotherapeutic trials (iRECIST). New lesions that are injected can be evaluated as part of the iterative assessment process for injected lesions but may not contribute to the target noninjected (T-NI) tumor burden. PD, progressive disease; NT-I, nontarget injected; NT-NI, nontarget noninjected; T-I, target injected.
FIG 5.
FIG 5.
Sample double waterfall plot. This sample double waterfall plot shows the quantitative best response (maximal reduction in tumor burden) in the target noninjected and target injected lesions for each participant in a trial, in order of the maximal effect on the noninjected lesions.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Amgen: FDA approves IMLYGIC (talimogene laherparepvec) as first oncolytic viral therapy in the US. https://www.amgen.com/media/news-releases/2015/10/fda-approves-imlygic-t...
    1. Andtbacka RH, Kaufman HL, Collichio F, et al. Talimogene laherparepvec improves durable response rate in patients with advanced melanoma. J Clin Oncol. 2015;33:2780–2788. - PubMed
    1. Harrington KJ, Andtbacka RH, Collichio F, et al. Efficacy and safety of talimogene laherparepvec versus granulocyte-macrophage colony-stimulating factor in patients with stage IIIB/C and IVM1a melanoma: Subanalysis of the Phase III OPTiM trial. OncoTargets Ther. 2016;9:7081–7093. - PMC - PubMed
    1. Andtbacka RH, Ross M, Puzanov I, et al. Patterns of clinical response with talimogene laherparepvec (T-VEC) in patients with melanoma treated in the OPTiM phase III clinical trial. Ann Surg Oncol. 2016;23:4169–4177. - PMC - PubMed
    1. Kaufman HL, Andtbacka RHI, Collichio FA, et al. Durable response rate as an endpoint in cancer immunotherapy: Insights from oncolytic virus clinical trials. J Immunother Cancer. 2017;5:72. - PMC - PubMed

Publication types