Dow‐Mu Koh

Patient-derived organoids (PDOs) have recently emerged as robust preclinical models; however, their potential to predict clinical outcomes in patients has remained unclear. We report on a living biobank of PDOs from metastatic, heavily pretreated colorectal and gastroesophageal cancer patients recruited in phase 1/2 clinical trials. Phenotypic and genotypic profiling of PDOs showed a high degree of similarity to the original patient tumors. Molecular profiling of tumor organoids was matched to drug-screening results, suggesting that PDOs could complement existing approaches in defining cancer vulnerabilities and improving treatment responses. We compared responses to anticancer agents ex vivo in organoids and PDO-based orthotopic mouse tumor xenograft models with the responses of the patients in clinical trials. Our data suggest that PDOs can recapitulate patient responses in the clinic and could be implemented in personalized medicine programs.

On May 3, 2008, a National Cancer Institute (NCI)-sponsored open consensus conference was held in Toronto, Ontario, Canada, during the 2008 International Society for Magnetic Resonance in Medicine Meeting. Approximately 100 experts and stakeholders summarized the current understanding of diffusion-weighted magnetic resonance imaging (DW-MRI) and reached consensus on the use of DW-MRI as a cancer imaging biomarker. DW-MRI should be tested as an imaging biomarker in the context of well-defined clinical trials, by adding DW-MRI to existing NCI-sponsored trials, particularly those with tissue sampling or survival indicators. Where possible, DW-MRI measurements should be compared with histologic indices including cellularity and tissue response. There is a need for tissue equivalent diffusivity phantoms; meanwhile, simple fluid-filled phantoms should be used. Monoexponential assessments of apparent diffusion coefficient values should use two b values (>100 and between 500 and 1000 mm2/sec depending on the application). Free breathing with multiple acquisitions is superior to complex gating techniques. Baseline patient reproducibility studies should be part of study designs. Both region of interest and histogram analysis of apparent diffusion coefficient measurements should be obtained. Standards for measurement, analysis, and display are needed. Annotated data from validation studies (along with outcome measures) should be made publicly available. Magnetic resonance imaging vendors should be engaged in this process. The NCI should establish a task force of experts (physicists, radiologists, and oncologists) to plan, organize technical aspects, and conduct pilot trials. The American College of Radiology Imaging Network infrastructure may be suitable for these purposes. There is an extraordinary opportunity for DW-MRI to evolve into a clinically valuable imaging tool, potentially important for drug development.

OBJECTIVE: In this article, we present the basic principles of diffusion-weighted imaging (DWI) that can aid radiologists in the qualitative and quantitative interpretation of DW images. However, a detailed discussion of the physics of DWI is beyond the scope of this article. A short discussion ensues on the technical aspects of performing DWI in the body. The emerging applications of DWI for tumor detection, tumor characterization, distinguishing tumor tissue from nontumor tissue, and monitoring and predicting treatment response are highlighted. The challenges to widespread adoption of the technique for cancer imaging in the body are discussed. CONCLUSION: DWI derives its image contrast from differences in the motion of water molecules between tissues. Such imaging can be performed quickly without the need for the administration of exogenous contrast medium. The technique yields qualitative and quantitative information that reflects changes at a cellular level and provides unique insights about tumor cellularity and the integrity of cell membranes. Recent advances enable the technique to be widely applied for tumor evaluation in the abdomen and pelvis and have led to the development of whole-body DWI.

Magnetic resonance (MR) imaging plays an increasingly important role in the evaluation of patients with liver disease because of its high contrast resolution, lack of ionizing radiation, and the possibility of performing functional imaging sequences. With advances in hardware and coil systems, diffusion-weighted (DW) MR imaging can now be applied to liver imaging with improved image quality. DW MR imaging enables qualitative and quantitative assessment of tissue diffusivity (apparent diffusion coefficient) without the use of gadolinium chelates, which makes it a highly attractive technique, particularly in patients with severe renal dysfunction at risk for nephrogenic systemic fibrosis. In this review, acquisition parameters, postprocessing, and quantification methods applied to liver DW MR imaging will be discussed. The current clinical uses of DW MR imaging (liver lesion detection and characterization, compared and combined with conventional sequences) and the emerging applications of DW MR imaging (tumor treatment response and diagnosis of liver fibrosis and cirrhosis) will be reviewed. Also, limitations, mainly image quality and reproducibility of diffusion parameters, and future directions of liver DW MR imaging will be discussed.