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Treatment Response Assessment
Atif Zaheer, MD
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KEY FACTS

  • Terminology

    • Imaging

      TERMINOLOGY

      • Definitions

        • Common terminology to describe tumor response to therapy
      • WHO Criteria

        • Assesses tumor burden
        • Tumor size measured by multiplying longest diameter (LD) of tumor by its greatest perpendicular diameter
        • Limitations
          • Reproducibility
          • Only tumor size used as metric and does not take into account tumor necrosis
          • No standard criteria for minimum or maximum number of lesions
      • Response Evaluation Criteria in Solid Tumors (RECIST) 1.0

        • Lesions must be ≥ 2 cm with radiography or ≥ 1 cm with CT
        • 1-dimensional measurement that calculates sum of LDs of all target tumor lesions
        • ≥ 5 lesions/organ and 10 lesions total can be measured
        • WHO and RECIST 1.0 criteria can detect response to treatment as early as 7-8 months
        • Limitations
          • Reproducibility
          • Differentiation of viable tumor from necrosis not done
          • Infiltrative tumor not measured accurately because of ill-defined margins
          • Not well defined for lymph node evaluation
      • RECIST 1.1

        • Total number of assessed lesions: 2/organ and total of 5
        • Lymph nodes with short axis ≥ 15 mm as target lesion
        • New guideline to use F-18 FDG PET for detecting new lesions
        • Limitations
          • Unidimensional measurement and considers all tumors to be spherical
          • Subjectivity
          • Tumor necrosis not addressed as part of response criteria
            • Issue especially with immunotherapy
          • No specific phase defined after IV contrast agent injection for lesion measurement
      • Modified CT Response Evaluation Criteria (Choi Criteria)

        • Developed in 2007 to assess GI stromal tumor response to imatinib treatment
        • Used for hypervascular tumors like GI stromal tumor (GIST), hepatocellular carcinoma (HCC)
        • May be superior to WHO and RECIST in predicting overall survival in HCC patients treated by Sorafenib and transarterial radioembolization
        • CT attenuation coefficient is measured by region of interest placement on lesions during portal venous phase
      • Response Evaluation Criteria in Cancer of Liver (RECICL)

        • RECICL evaluate HCC response to locoregional therapy (LRT)
        • Posttreatment assessment by imaging is recommended 1 month after transarterial chemoembolization (TACE) and 6 months after transarterial radioembolization
        • Quantifies necrotic parts using bidimensional measurements like WHO
      • European Association for Study of Liver (EASL) Criteria

        • To address limitations of size-based criteria in assessing tumor response to LRT
        • Like WHO bidimensional measurements but only focuses on viable tumor tissue (sum of arterially enhancing part of tumor)
        • May detect tumor response as early as 1.6 months after therapy
        • Can predict overall survival between 2 and 3 months after TACE
      • Modified RECIST (mRECIST)

        • Combined some features of EASL criteria with RECIST criteria
        • LD of enhancing part of tumor in arterial phase of CT or MR without taking into account necrotic part
        • Poorly or atypically enhancing HCC cannot be selected as target lesions
        • Assesses tumor response as early as 2 months
      • Immune-Related Criteria

        • Used for treatment response after immune therapies
        • Overall tumor burden at baseline is determined as sum of product of diameters for all index lesions
        • Initial enlargement and development of new lesions not considered progressive disease (due to T-cell infiltration)

      IMAGING

      • CT Findings

        • MR Findings

          • Nuclear Medicine Findings

            Selected References

            1. Nishino M: Therapy Response Imaging in Oncology. Springer, 2020
            2. Somarouthu B et al: Immune-related tumour response assessment criteria: a comprehensive review. Br J Radiol. 91(1084):20170457, 2018
            3. Sung PS et al: 18F-fluorodeoxyglucose uptake of hepatocellular carcinoma as a prognostic predictor in patients with sorafenib treatment. Eur J Nucl Med Mol Imaging. 45(3):384-91, 2018
            4. Lencioni R et al: Objective response by mRECIST as a predictor and potential surrogate end-point of overall survival in advanced HCC. J Hepatol. 66(6):1166-72, 2017
            5. Shirota N et al: Intravoxel incoherent motion MRI as a biomarker of sorafenib treatment for advanced hepatocellular carcinoma: a pilot study. Cancer Imaging. 16:1, 2016
            6. Syha R et al: Parenchymal blood volume assessed by C-arm-based computed tomography in immediate posttreatment evaluation of drug-eluting bead transarterial chemoembolization in hepatocellular carcinoma. Invest Radiol. 51(2):121-6, 2016
            7. Yang Z et al: Application of single voxel 1H magnetic resonance spectroscopy in hepatic benign and malignant lesions. Med Sci Monit. 22:5003-10, 2016
            8. Bonekamp D et al: Interobserver agreement of semi-automated and manual measurements of functional MRI metrics of treatment response in hepatocellular carcinoma. Eur J Radiol. 83(3):487-96, 2014
            9. Gonzalez-Guindalini FD et al: Assessment of liver tumor response to therapy: role of quantitative imaging. Radiographics. 33(6):1781-800, 2013
            10. Kudo M et al: Response Evaluation Criteria in Cancer of the Liver (RECICL) proposed by the Liver Cancer Study Group of Japan (2009 revised version). Hepatol Res. 40(7):686-92, 2010
            11. Lencioni R et al: Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis. 30(1):52-60, 2010
            12. Choi H et al: Correlation of computed tomography and positron emission tomography in patients with metastatic gastrointestinal stromal tumor treated at a single institution with imatinib mesylate: proposal of new computed tomography response criteria. J Clin Oncol. 25(13):1753-9, 2007
            Related Anatomy
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            References
            Tables

            Tables

            KEY FACTS

            • Terminology

              • Imaging

                TERMINOLOGY

                • Definitions

                  • Common terminology to describe tumor response to therapy
                • WHO Criteria

                  • Assesses tumor burden
                  • Tumor size measured by multiplying longest diameter (LD) of tumor by its greatest perpendicular diameter
                  • Limitations
                    • Reproducibility
                    • Only tumor size used as metric and does not take into account tumor necrosis
                    • No standard criteria for minimum or maximum number of lesions
                • Response Evaluation Criteria in Solid Tumors (RECIST) 1.0

                  • Lesions must be ≥ 2 cm with radiography or ≥ 1 cm with CT
                  • 1-dimensional measurement that calculates sum of LDs of all target tumor lesions
                  • ≥ 5 lesions/organ and 10 lesions total can be measured
                  • WHO and RECIST 1.0 criteria can detect response to treatment as early as 7-8 months
                  • Limitations
                    • Reproducibility
                    • Differentiation of viable tumor from necrosis not done
                    • Infiltrative tumor not measured accurately because of ill-defined margins
                    • Not well defined for lymph node evaluation
                • RECIST 1.1

                  • Total number of assessed lesions: 2/organ and total of 5
                  • Lymph nodes with short axis ≥ 15 mm as target lesion
                  • New guideline to use F-18 FDG PET for detecting new lesions
                  • Limitations
                    • Unidimensional measurement and considers all tumors to be spherical
                    • Subjectivity
                    • Tumor necrosis not addressed as part of response criteria
                      • Issue especially with immunotherapy
                    • No specific phase defined after IV contrast agent injection for lesion measurement
                • Modified CT Response Evaluation Criteria (Choi Criteria)

                  • Developed in 2007 to assess GI stromal tumor response to imatinib treatment
                  • Used for hypervascular tumors like GI stromal tumor (GIST), hepatocellular carcinoma (HCC)
                  • May be superior to WHO and RECIST in predicting overall survival in HCC patients treated by Sorafenib and transarterial radioembolization
                  • CT attenuation coefficient is measured by region of interest placement on lesions during portal venous phase
                • Response Evaluation Criteria in Cancer of Liver (RECICL)

                  • RECICL evaluate HCC response to locoregional therapy (LRT)
                  • Posttreatment assessment by imaging is recommended 1 month after transarterial chemoembolization (TACE) and 6 months after transarterial radioembolization
                  • Quantifies necrotic parts using bidimensional measurements like WHO
                • European Association for Study of Liver (EASL) Criteria

                  • To address limitations of size-based criteria in assessing tumor response to LRT
                  • Like WHO bidimensional measurements but only focuses on viable tumor tissue (sum of arterially enhancing part of tumor)
                  • May detect tumor response as early as 1.6 months after therapy
                  • Can predict overall survival between 2 and 3 months after TACE
                • Modified RECIST (mRECIST)

                  • Combined some features of EASL criteria with RECIST criteria
                  • LD of enhancing part of tumor in arterial phase of CT or MR without taking into account necrotic part
                  • Poorly or atypically enhancing HCC cannot be selected as target lesions
                  • Assesses tumor response as early as 2 months
                • Immune-Related Criteria

                  • Used for treatment response after immune therapies
                  • Overall tumor burden at baseline is determined as sum of product of diameters for all index lesions
                  • Initial enlargement and development of new lesions not considered progressive disease (due to T-cell infiltration)

                IMAGING

                • CT Findings

                  • MR Findings

                    • Nuclear Medicine Findings

                      Selected References

                      1. Nishino M: Therapy Response Imaging in Oncology. Springer, 2020
                      2. Somarouthu B et al: Immune-related tumour response assessment criteria: a comprehensive review. Br J Radiol. 91(1084):20170457, 2018
                      3. Sung PS et al: 18F-fluorodeoxyglucose uptake of hepatocellular carcinoma as a prognostic predictor in patients with sorafenib treatment. Eur J Nucl Med Mol Imaging. 45(3):384-91, 2018
                      4. Lencioni R et al: Objective response by mRECIST as a predictor and potential surrogate end-point of overall survival in advanced HCC. J Hepatol. 66(6):1166-72, 2017
                      5. Shirota N et al: Intravoxel incoherent motion MRI as a biomarker of sorafenib treatment for advanced hepatocellular carcinoma: a pilot study. Cancer Imaging. 16:1, 2016
                      6. Syha R et al: Parenchymal blood volume assessed by C-arm-based computed tomography in immediate posttreatment evaluation of drug-eluting bead transarterial chemoembolization in hepatocellular carcinoma. Invest Radiol. 51(2):121-6, 2016
                      7. Yang Z et al: Application of single voxel 1H magnetic resonance spectroscopy in hepatic benign and malignant lesions. Med Sci Monit. 22:5003-10, 2016
                      8. Bonekamp D et al: Interobserver agreement of semi-automated and manual measurements of functional MRI metrics of treatment response in hepatocellular carcinoma. Eur J Radiol. 83(3):487-96, 2014
                      9. Gonzalez-Guindalini FD et al: Assessment of liver tumor response to therapy: role of quantitative imaging. Radiographics. 33(6):1781-800, 2013
                      10. Kudo M et al: Response Evaluation Criteria in Cancer of the Liver (RECICL) proposed by the Liver Cancer Study Group of Japan (2009 revised version). Hepatol Res. 40(7):686-92, 2010
                      11. Lencioni R et al: Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis. 30(1):52-60, 2010
                      12. Choi H et al: Correlation of computed tomography and positron emission tomography in patients with metastatic gastrointestinal stromal tumor treated at a single institution with imatinib mesylate: proposal of new computed tomography response criteria. J Clin Oncol. 25(13):1753-9, 2007