Interobserver Variability in CT-based Morphologic Tumor Response Assessment of Colorectal Liver Metastases
Nina J. Wesdorp, Ruby Kemna, Karen Bolhuis, Jan H. T. M. van Waesberghe, Irene M. G. C. Nota, Femke Struik, Ikrame Oulad Abdennabi, Saffire S. K. S. Phoa, Susan van Dieren, Martinus J. van Amerongen, Thiery Chapelle, Cornelis H. C. Dejong, Marc R. W. Engelbrecht, Michael F. Gerhards, Dirk Grünhagen, Thomas M. van Gulik, John J. Hermans, Koert P. de Jong, Joost M. Klaase, Mike S. L. Liem, Krijn P. van Lienden, I. Quintus Molenaar, Gijs A. Patijn, Arjen M. Rijken, Theo M. Ruers, Cornelis Verhoef, Johannes H. W. de Wilt, Rutger-Jan Swijnenburg, Cornelis J. A. Punt, Joost Huiskens, Jaap Stoker, Geert Kazemier
Radiology: Imaging Cancer https://doi.org/10.1148/rycan.210105
Colorectal cancer is one of the most common malignant neoplasms, ranking 2nd to 4th in terms of incidence globally (1). More than half of patients with colorectal cancer develop colorectal liver metastases (CRLM). Only 20% of these patients are eligible for curative therapy (resection and/or ablation). The remaining patients with CRLM most often receive systemic treatment to suppress the tumour load for secondary local treatment or in a palliative setting. The advent of targeted therapies such as bevacizumab and panitumumab has improved these patients’ outcomes.
Using size-based radiologic parameters, the RECIST 1.1 criteria are widely applied to evaluate tumour response to treatment. However, therapy induces not only size changes but also morphologic modifications.
This study evaluates interobserver variability in morphologic tumour response assessment according to set criteria in participants with CRLM treated with systemic therapy. The relation of morphologic tumour response with RAS/BRAF mutation status and targeted therapy, and the comparison of morphologic tumour response with the RECIST 1.1 measurements were secondary objectives.
The authors used a sample of 369 patients (from the CAIRO5 trial) with initially unresectable colorectal cancer with liver-only metastases. These patients were followed in one of the 54 medical centers included in the trial.
Exclusion criteria were: more than 15 CRLM at baseline or first follow-up CT examination, missing baseline or first follow-up CT, incomplete CT examination, technical error in diagnostic software and the use of MRI or PET with non–contrast-enhanced CT. This resulted in a sample of 156 patients. In addition, three other patients were excluded due to the presence of calcifications or the reduced size of lesions.
All the 153 patients in the final sample did a contrast-enhanced CT scan at baseline and at every two months during systemic therapy. Only the baseline and first follow-up CT scans in the portal venous phase were included in the current study.
Tumour response to systemic therapy was evaluated according to the morphologic criteria formulated by Chun et al (2). Morphology group 3 was characterized by heterogeneous attenuation and ill-defined tumour–liver interface, with or without peripheral rim enhancement. Morphology group 1 was described as homogeneous and low attenuation, with a sharply defined tumour–liver interface and an absence of peripheral rim enhancement. Morphology group 2 tumours could not be assigned to morphology group 1 or group 3 and were described as mixed attenuation, variable tumour–liver interface, and, if initially present, partially resolved rim enhancement. The morphologic response was defined as an optimal response if there was a change from either group 2 or 3 to group 1; a suboptimal response if there was a change from group 3 to 2; and no response if the morphology group did not change or moved to a higher group.
According to those criteria, three radiologists independently assessed tumour response on the baseline and first follow-up CT scans. Two additional radiologists evaluated disagreement cases. Interobserver agreement was calculated using Fleiss k.
Morphologic assessment performed by the three radiologists yielded 86 (56%) agreement cases and 67 (44%) disagreement cases (including four major disagreement cases). Overall interobserver agreement between the panel radiologists on morphology groups and morphologic response categories was moderate (k = 0.53, 95% CI: 0.48, 0.58 and k = 0.54, 95% CI: 0.47, 0.60, respectively). Optimal morphologic response was particularly observed in patients treated with bevacizumab (P = 0.001) and in patients with RAS/BRAF mutation (P = 0.04). No evidence of a relationship between RECIST 1.1 and morphologic response was found (P = 0.61).
Some limitations should be considered in this study. First, the CT scans were acquired in one of 54 medical centres, in different devices and with different protocols. Besides, the selection of participants with initially unresectable CRLM might have influenced the results. Furthermore, the criteria used for morphologic evaluation are not objective, mainly in group 2. Additionally, evaluating small lesions according to the proposed parameters is difficult.
There is also a lack of studies evaluating the relationship between morphologic tumour response and histopathologic or survival outcomes.
In conclusion, the morphologic response of liver metastasis to chemotherapy can be clinically relevant, as considering only the size of lesions can underestimate response. Despite that, objective response parameters should be defined to improve the interobserver variability.
References:
- Sawicki, T., Ruszkowska, M., Danielewicz, A., Niedźwiedzka, E., Arłukowicz, T., & Przybyłowicz, K. E. (2021). A Review of Colorectal Cancer in Terms of Epidemiology, Risk Factors, Development, Symptoms and Diagnosis. Cancers, 13(9), 2025. https://doi.org/10.3390/cancers13092025
- Chun, Y. S. (2009). Association of Computed Tomography Morphologic Criteria With Pathologic Response and Survival in Patients Treated With Bevacizumab for Colorectal Liver Metastases. JAMA, 302(21), 2338. https://doi.org/10.1001/jama.2009.1755
Vasco Ferrão Mendes is a third-year radiology resident at Centro Hospitalar e Universitário de Coimbra, Portugal. From the city of Famalicão, he graduated from the University of Porto in 2018. Vasco has a broad range of interests in diagnostic imaging, including abdominal imaging in various imaging techniques such as CT and ultrasonography. He is a member of various societies such as SPRMN (Sociedade Portuguesa de Radiologia e Medicina Nuclear), RSNA (Radiology Society of North America) and ESR (European Society of Radiology).
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