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.
OBJECTIVE
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.


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.
Dept. of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands; The Royal Marsden NHS Foundation Trust, Breast Unit, London, United Kingdom. Electronic address: gaia.schiavon@icr.ac.uk.
Gaia
G
Schiavon
Dept. of Radiology, Erasmus University Medical Center, Rotterdam, The Netherlands; Dept. of Radiology, Addenbrooke's Hospital, Cambridge, United Kingdom.
Alessandro
A
Ruggiero
TNO Technical Sciences, The Hague, The Netherlands.
Dave J
DJ
Bekers
The Royal Marsden NHS Foundation Trust, Breast Unit, London, United Kingdom.
Peter A
PA
Barry
Dept. of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
Stefan
S
Sleijfer
Dept. of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
Jaqueline
J
Kloth
Dept. of Radiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Gabriel P
GP
Krestin
Dept. of General Medical Oncology, KU Leuven, Leuven Cancer Institute, Leuven, Belgium.
Patrick
P
Schöffski
Dept. of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
Jaap
J
Verweij
Dept. of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
Ron H J
RH
Mathijssen
D001549:Benzamides / Q000627:therapeutic use*; D015331:Cohort Studies; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D000068877:Imatinib Mesylate; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary; D015588:Observer Variation; D017063:Outcome Assessment, Health Care / Q000379:methods; D010879:Piperazines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D047368:Tumor Burden / Q000187:drug effects
D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate
3D; Elongation; GIST; Imatinib; Liver metastases; Morphology; Orientation; RECIST; Response; Volume