Changes in Daily Apparent Diffusion Coefficient on Fully Quantitative Magnetic Resonance Imaging Correlate With Established Genomic Pathways of Radiation Sensitivity and Reveal Novel Biologic Associations.

Autor:	Hall WA; Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin. Electronic address: whall@mcw.edu., Mathison AJ; Linda T. and John A. Mellowes Center for Genomic Sciences and Precision Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin; Department of Surgery, Division of Research, Medical College of Wisconsin, Milwaukee, Wisconsin., DeVoe E; Linda T. and John A. Mellowes Center for Genomic Sciences and Precision Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin., Tschannen M; Linda T. and John A. Mellowes Center for Genomic Sciences and Precision Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin., Wendt-Andrae J; Linda T. and John A. Mellowes Center for Genomic Sciences and Precision Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin., Straza M; Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin., Awan M; Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin., Puckett LL; Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin., Lawton CAF; Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin., Schultz C; Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin., Urrutia R; Linda T. and John A. Mellowes Center for Genomic Sciences and Precision Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin; Department of Surgery, Division of Research, Medical College of Wisconsin, Milwaukee, Wisconsin; Department of Biochemistry, Medical College of Wisconsin, Milwaukee, Wisconsin., Kerns S; Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin., Torres-Roca JF; Department of Radiation Oncology and Bioinformatics, Moffitt Cancer Center, Tampa, Florida., Li XA; Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin., Erickson B; Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin., Nevalainen MT; Department of Pathology, Medical College of Wisconsin, Milwaukee, Wisconsin., Zimmermann MT; Linda T. and John A. Mellowes Center for Genomic Sciences and Precision Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin; Department of Biochemistry, Medical College of Wisconsin, Milwaukee, Wisconsin; Clinical and Translational Sciences Institute, Medical College of Wisconsin, Milwaukee, Wisconsin., Paulson E; Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin.
Jazyk:	angličtina
Zdroj:	International journal of radiation oncology, biology, physics [Int J Radiat Oncol Biol Phys] 2024 Oct 01; Vol. 120 (2), pp. 570-578. Date of Electronic Publication: 2024 May 29.
DOI:	10.1016/j.ijrobp.2024.03.042
Abstrakt:	Purpose: Changes in quantitative magnetic resonance imaging (qMRI) are frequently observed during chemotherapy or radiation therapy (RT). It is hypothesized that qMRI features are reflective of underlying tissue responses. It's unknown what underlying genomic characteristics underly qMRI changes. We hypothesized that qMRI changes may correlate with DNA damage response (DDR) capacity within human tumors. Therefore, we designed the current study to correlate qMRI changes from daily RT treatment with underlying tumor transcriptomic profiles. Methods and Materials: Study participants were prospectively enrolled (National Clinical Trial 03500081). RNA expression levels for 757 genes from pretreatment biopsies were obtained using a custom panel that included signatures of radiation sensitivity and DDR. Daily qMRI data were obtained from a 1.5 Tesla MR linear accelerator. Using these images, d-slow, d-star, perfusion, and apparent diffusion coefficient-mean values in tumors were plotted per-fraction, over time, and associated with genomic pathways. Results: A total of 1022 qMRIs were obtained from 39 patients and both genomic data and qMRI data from 27 total patients. For 20 of those patients, we also generated normal tissue transcriptomic data. Radio sensitivity index values most closely associated with tissue of origin. Multiple genomic pathways including DNA repair, peroxisome, late estrogen receptor responses, KRAS signaling, and UV response were significantly associated with qMRI feature changes (P < .001). Conclusions: Genomic pathway associations across metabolic, RT sensitivity, and DDR pathways indicate common tumor biology that may correlate with qMRI changes during a course of treatment. Such data provide hypothesis-generating novel mechanistic insight into the biologic meaning of qMRI changes during treatment and enable optimal selection of imaging biomarkers for biologically MR-guided RT. (Published by Elsevier Inc.)
Databáze:	MEDLINE
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