Tumor Response Assessment

Tumor Response Assessment

Overview

  • Radiologists are commonly asked to assess the effect of anti-cancer agents on tumor burden. This is achieved by the measurement of tumor lesions on baseline and follow-up imaging studies and overall response assessment at each timepoint according to widely accepted response criteria.
  • In order to accurately characterize response to treatment with the appropriate response criteria, it is necessary to know
    • The malignancy
    • Type of therapy administered

It is also helpful to know

  • When the therapy was initiated
  • A sense of the ongoing clinical picture, which may be obtained from ordering information and/or oncology provider notes.

Anatomic Criteria: RECIST 1.1

  • Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) is the most commonly employed imaging response assessment. This can be applied to any malignancy treated with any agent. Response assessment is rendered based upon changes in target and non-target lesions.
  • Response assessment is based on the change of the sum diameter of target lesions over time (long axes of target masses + short axes of target nodes). Timepoint sum diameters are compared to the baseline sum diameter or the nadir sum diameter (whichever is smaller).
  • Eisenhauer EA, Therasse P, Bogaerts J et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47.

Measurable Target Lesions

  • Max 2 per organ, 5 total
  • Solid organ masses measure at least 10 mm in long axis diameter
  • Lymph nodes measure at least 15 mm in short axis
  • Bone lesions with soft tissue component >10 mm can be measurable
  • Cystic metastases can be used, though solid lesions are preferred if present
  • Are easily measured/ reproduced
  • Have not been previously irradiated or subject to prior locoregional therapy
Measurable target lesions

Non-Target Lesions

  • all other lesions (small <10 mm or pathological nodes with short axis >10 mm but <15 mm)
  • lesions not easily measured including ascites, pleural or pericardial effusion, lymphangitic spread in lung, leptomeningeal disease
Non-target lesions

Complete Response (CR)

  • Disappearance of all targets
  • Disappearance of all non-target disease
  • Pathological nodes <10 mm in short axis

Partial Response (PR)

  • At least 30% decrease in the sum diameter of target lesions, taking as reference the baseline sum diameter
  • Persistence of 1 or more non-target lesions (non-PD), or not all evaluated
Partial Response
Metastatic pancreatic cancer (baseline)
Partial Response
Metastatic pancreatic cancer (follow-up with deep PR)

Stable Disease (SD)

  • Neither PR nor PD
  • Persistence of 1 or more non-targets (non-PD) or not all evaluated
Stable Disease Stable Disease
Waldenstrom’s Macroglobulinemia (baseline) Waldenstrom’s Macroglobulinemia (follow-up with SD)

Progressive Disease (PD)

  • New lesion, or
  • At least 20% increase in the sum diameters of the target lesions, taking as reference the smallest sum on study (baseline or nadir)
  • Absolute increase in the sum diameter of targets of at least 5 mm
  • Unequivocal progression of NTD (not modest increase)
Progressive Disease Progressive Disease
Metastatic leiomyosarcoma (baseline) Metastatic leiomyosarcoma (follow-up with PD)

Morphologic Criteria: Choi Criteria

Choi H, Charnsangavej C, Faria SC 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. 2007 May 1;25(13):1753-9.

Malignancies which may be assessed by this method

  • Gastrointestinal Stromal Tumor (GIST) treated with imatinib, sunitinib, regorafenib
  • Other sarcomas
  • Renal cell carcinoma treated with Vascular Endothelial Growth Factor (VEGF) targeted therapy

Tumor Measurements

  • Longest cross-sectional dimension of each lesion; sum long axis diameter calculated
  • CT density of each tumor measured by drawing a region of interest around the margin of the entire tumor; mean HU calculated for each patient

Complete Response (CR)

  • Disappearance of all lesions
  • No new lesions

Partial Response (PR)

  • Decrease in size of at least 10% or a decrease in density (HU) of at least 15% on CT;
  • No new lesions or obvious progression of nonmeasurable disease
Choi Criteria - Partial Response (PR):
Gastrointestinal Stromal Tumor (baseline) and follow-up (with PR on imatinib)
Choi Criteria - Partial Response (PR) Metastatic renal cell cancer
Metastatic renal cell cancer (baseline) and follow-up (with PR to sunitinib)

Stable Disease (SD)

  • Does not meet CR, PR, PD

Progressive Disease (PD)

  • An increase in tumor size of at least 10% and does not meet criteria of PR by tumor density (HU) on CT, or
  • New lesions, or
  • New intratumoral nodules or increase in the size of the existing tumoral nodules
Choi Criteria, Progressive Disease (PD):, Metastatic GIST
Metastatic GIST (baseline)

Choi Criteria, Progressive Disease (PD), Metastatic GIST with new intratumoral nodule
Metastatic GIST with new intratumoral nodule (PD by Choi, arrowhead)

Pitfalls

  • Intratumoral hemorrhage mimicking tumor progression
Choi Criteria, PItfalls, Metastatic GIST

Metastatic GIST (baseline)

Choi Criteria, Pitfalls, GIST treated with sunitinib

GIST treated with sunitinib; right hepatic lesion likely demonstrates intratumoral hemorrhage with a fluid-fluid level, a potential pitfall not to be mistaken for increasing disease

Other Criteria
Partial Response (PR): according to CT morphologic criteria

  • Decreased size and density, increased homogeneity and better marginated liver metastases in colon cancer treated with a bevacizumab-containing regimen
  • Principles of morphologic assessment can be applied for assessment anytime a patient is treated with anti-angiogenic treatment
  • Chun YS Vauthey J, Boonsirikamchai P et al. Association of Computed Tomography Morphologic Criteria With Pathologic Response and Survival in Patients Treated With Bevacizumab for Colorectal Liver Metastases. JAMA. 2009; 302(21):2338-2344.
Partial Response (PR), Metastatic colon cancer

Metastatic colon cancer (baseline)Partial Response (PR), Metastatic colon cancer with PR
Metastatic colon cancer with PR according to CT morphologic criteria treated with FOLFOX and bevacizumab

Immune Response Assessment: iRECIST

  • “I” indicates immune responses assigned using iRECIST
  • Seymour L, Bogaerts J, Perrone A et al. iRECIST: guidelines for response criteria for use in trials testing immunotherapeutics. Lancet Oncol. 2017 Mar; 18(3): e143–e152.

Target Lesion Selection and Measurement

  • No change from RECIST 1.1 in target and nontarget definitions, numbers and sites of disease

Unique Features of Immune Response Assessment

New lesions

  • are recorded separately and not included in the sum diameter of lesions
  • result in iUPD
  • on subsequent assessment after iUPD, additional new lesions or an increased size of previously new lesions (at least 5 mm for sum of new target lesion or any increase in new non-target lesion), results in iCPD

Confirmation of Progressive Disease

  • If iUPD criteria met and the patient is clinically stable, treatment often continues and 4-8 week follow-up imaging is performed to assess for transient pseudoprogression or true progression
  • If iUPD criteria met on basis of progression in target or non-target disease, then 4-8 week follow-up also  indicated to assess for iCPD

Complete Response (iCR)

  • Disappearance of all targets
  • Disappearance of non-target disease
  • Pathological nodes <10 mm in short axis
iRECIST, Complete Response (iCR), Metastatic melanoma to liver and peritoneum

Metastatic melanoma to liver and peritoneum (baseline)

iRECIST, Complete Response (iCR), Metastatic melanoma with iCR to ipilimumab and nivolumab

Metastatic melanoma with iCR to ipilimumab and nivolumab

Partial Response (iPR)

  • At least 30% decrease in the sum diameter of target lesions, taking as reference the baseline sum diameter
  • Persistence of 1 or more non-target lesions (non-iCR/non-iUPD)
  • For patients with NTD only at baseline, only iCR or non-iCR/ non-IUPD can be assigned
iRECIST, Partial Response (iPR), Metastatic melanoma

Metastatic melanoma (baseline)

iRECIST, Partial Response (iPR), Metastatic melanoma with iPR to ipilimumab and nivolumab

Metastatic melanoma with iPR to ipilimumab and nivolumab

Stable Disease (iSD)

  • Neither PR nor PD
  • Persistence of 1 or more non-targets (non-iCR/non-iUPD)
  • No new lesion

Unconfirmed Progression (iUPD)

  • is defined by RECIST 1.1 criteria for progressive disease
  • New lesion or at least 20% increase in the sum diameters of the target lesions, taking as reference the smallest sum on study (baseline or nadir)
  • Unequivocal progression of non target disease (not modest increase)
  • Absolute target increase in the sum diameter of targets of at least 5 mm
  • Treatment is often continued for 4-8 weeks if the patient is clinically stable with short interval follow-up scan advised
  • Subsequent assessments may result in iCR, iPR, iSD, iUPD (again), or iCPD
  • iUPD can be assigned multiple times as long as iCPD does not occur
Unconfirmed Progression (iUPD), Baseline Baseline (A)
Unconfirmed Progression (iUPD), 1st follow-up 1st follow-up (B)
Unconfirmed Progression (iUPD), 2nd follow-up 2nd follow-up (C)

Metastatic renal cell carcinoma (A) treated with an immune checkpoint inhibitor, with increased L retroperitoneal disease on first follow-up resulting in iUPD (B) and decreased disease on second follow-up (C), resulting in subsequent iPR.

Figure from Cancer Immunol Res. 2016 Jan;4(1):12-7.

Confirmed Progression (iCPD)

  • Further increase in the sum diameters of the target lesions, taking as reference the smallest sum on study (baseline or nadir), additional new lesion since iUPD, and/ or increased size of new lesion(s) at iUPD
  • Further increase from iUPD
  • Absolute target increase in the sum diameter of targets of at least 5 mm
Confirmed Progression (iCPD), Baseline Baseline (A)       
Confirmed Progression (iCPD), 1st follow-up 1st follow-up (B
Confirmed Progression (iCPD), 2nd follow-up 2nd follow-up (C)

Metastatic renal cell carcinoma (A) treated with combination therapy including an immune checkpoint inhibitor, with increased LUQ peritoneal disease on first follow-up (B) and further increased disease on second follow-up (C), confirming progression (iCPD).

References

  • Eisenhauer EA, Therasse P, Bogaerts J et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47.
  • Choi H, Charnsangavej C, Faria SC 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. 2007 May 1;25(13):1753-9.
  • Chun YS Vauthey J, Boonsirikamchai P et al. Association of Computed Tomography Morphologic Criteria With Pathologic Response and Survival in Patients Treated With Bevacizumab for Colorectal Liver Metastases. JAMA. 2009; 302(21):2338-2344.
  • Seymour L, Bogaerts J, Perrone A et al. iRECIST: guidelines for response criteria for use in trials testing immunotherapeutics. Lancet Oncol. 2017 Mar; 18(3): e143–e152.