Imaging is widely applied as a biomarker in therapeutic clinical trials. It is commonly used to assess the response to therapeutic
interventions. However, the wealth of imaging modalities and techniques applicable for different diseases often make it difficult
for the clinical trial manager to choose the technique best suited for the underlying question.
This article describes the opportunities and challenges for the use of imaging in clinical trials from an imager's perspective—one
who has experience as a principal investigator, co-investigator, and core lab scientist.
Current assessment strategies
The most common use of imaging in clinical trials today is in the evaluation of tumor size. The two most commonly used evaluation
criteria are the World Health Organization (WHO)1,2 criteria and the Response Evaluation Criteria in Solid Tumors (RECIST)3 (see Figure 1). Both assessments are based on the measurement of one or two diameters of selected target lesions. Up to a maximum of five
lesions per organ and 10 lesions in total, representative of all involved organs, are identified as target lesions. The sum
of the longest diameter for all target lesions is calculated. The response to treatment is classified by the following criteria:
- The disappearance of all target lesions constitutes complete response.
- Partial response is a decrease of at least 30% in the sum of the longest diameters of the target lesions.
- An increase of at least 20% is considered progressive disease.
- Anything between partial response and progressive disease is labeled stable disease.
These evaluation criteria have been developed to estimate volume changes of lesions in response to therapy. This was necessary
because the assessment of the true lesion volume was very time consuming, since the lesions had to be outlined on every slice
manually. Therefore, it was not applicable in clinical routine. However, the assessment of diameters also has several drawbacks.
Its biggest limitation is its inaccuracy. As a result, the assessed changes have to be large in order to be considered truly
significant volume changes. For example, a 30% diameter decrease suggesting partial response is equal to a 65% volume decrease.
Therefore, the assessment of the true three-dimensional volume of all lesions is a much more sensitive response criteria.
Figure 1. Images of a male patient with liver metastases from colorectal cancer. The target lesion (arrow) (a) is measured
according to WHO criteria by measuring its longest diameter and the according longest orthogonal diameter. A semi-automatic
software segmented the tumor three-dimensionally (b), displaying three orthogonal planes.
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Computer algorithms have been developed to semi-automatically assess the tumor volume and are used in some clinical trials4,5 (see Figure 1). These algorithms have to be implemented in clinical routine. For clinical trials, the implementation of
such semi-automatic algorithms would mean that tumor response may be detected in a much earlier stage and, therefore, success
or failure of a treatment may be shown in a much shorter time frame. This would lower the costs of clinical trials significantly
because the need for follow-up examinations would be reduced due to the earlier achievement of study endpoints.
Innovative imaging procedures
Rapid scientific progress in imaging methodologies seems to be encouraging clinical researchers to use these methodologies
to address their needs in clinical trials. Highly specialized techniques such as diffusion tensor imaging,6 neurofunctional magnetic resonance imaging (fMRI),7 and dynamic contrast enhanced magnetic resonance imaging (DCE MRI)8,9 seem to be the answers to researchers' unaddressed needs.
