The effect of baseline morphology and its change during treatment on the accuracy of Response Evaluation Criteria in Solid Tumours in assessment of liver metastases

Eur J Cancer. 2014 Mar;50(5):972-80. doi: 10.1016/j.ejca.2014.01.004. Epub 2014 Jan 27.

Abstract

Purpose: Tumour response assessment to therapy is crucial in oncology. We analysed the morphology of liver metastases (LM) in gastrointestinal stromal tumour (GIST) patients to determine whether uni-dimensional measurement of lesions by Response Evaluation Criteria in Solid Tumours (RECIST), accurately reflects lesion volume.

Materials and methods: The volumes of LM (n=139) from a GIST patient cohort were measured using computed tomography (CT) at baseline, 3, 6 and 12 months after commencement of imatinib therapy. Baseline measurements were obtained by two independent investigators and inter-observer agreement assessed using Bland-Altman plots. Actual lesion volumes (V(ACTUAL)) were measured and compared with volumes based on the RECIST measure (V(RECIST)), and with volumes based on three orthogonal measures (V(ELLIPSOID)) at several time-points.

Results: At baseline, the inter-observer bias for V(ACTUAL) was just 1.8%. V(RECIST) and V(ELLIPSOID) overestimated V(ACTUAL) by a mean of 35% and only 9% respectively (P<0.0001 for both). At baseline, 44% (61/139) of LM were classified as spheroidal and 56% (78/139) as ellipsoidal. During treatment, only 42% of LM retained their original morphology. The remainder demonstrated significant changes in morphology (from spheroidal to ellipsoidal and vice versa) over time, while the RECIST measure did not reflect such changes.

Conclusions: The morphology of LM in GIST is rarely spherical (an underlying assumption for RECIST) and can change considerably during imatinib therapy. In this setting, measurements using RECIST do not reflect changes in size and morphology. Additionally, whilst V(ELLIPSOID) is a more suitable surrogate for volume estimation, it is still somewhat limited by the morphology and orientation of such lesions. Studies are warranted to further explore the clinical impact of these findings.

Keywords: 3D; Elongation; GIST; Imatinib; Liver metastases; Morphology; Orientation; RECIST; Response; Volume.

Publication types

  • Multicenter Study

MeSH terms

  • Benzamides / therapeutic use*
  • Cohort Studies
  • Gastrointestinal Stromal Tumors / drug therapy*
  • Gastrointestinal Stromal Tumors / pathology
  • Humans
  • Imatinib Mesylate
  • Liver / drug effects
  • Liver / pathology
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / secondary
  • Observer Variation
  • Outcome Assessment, Health Care / methods
  • Piperazines / therapeutic use*
  • Pyrimidines / therapeutic use*
  • Time Factors
  • Tomography, X-Ray Computed
  • Tumor Burden / drug effects

Substances

  • Benzamides
  • Piperazines
  • Pyrimidines
  • Imatinib Mesylate