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Diffusion MRI in early cancer therapeutic response assessment.

ABSTRACT: Imaging biomarkers for the predictive assessment of treatment response in patients with cancer earlier than standard tumor volumetric metrics would provide new opportunities to individualize therapy. Diffusion-weighted MRI (DW-MRI), highly sensitive to microenvironmental alterations at the cellular level, has been evaluated extensively as a technique for the generation of quantitative and early imaging biomarkers of therapeutic response and clinical outcome. First demonstrated in a rodent tumor model, subsequent studies have shown that DW-MRI can be applied to many different solid tumors for the detection of changes in cellularity as measured indirectly by an increase in the apparent diffusion coefficient (ADC) of water molecules within the lesion. The introduction of quantitative DW-MRI into the treatment management of patients with cancer may aid physicians to individualize therapy, thereby minimizing unnecessary systemic toxicity associated with ineffective therapies, saving valuable time, reducing patient care costs and ultimately improving clinical outcome. This review covers the theoretical basis behind the application of DW-MRI to monitor therapeutic response in cancer, the analytical techniques used and the results obtained from various clinical studies that have demonstrated the efficacy of DW-MRI for the prediction of cancer treatment response. Copyright © 2016 John Wiley & Sons, Ltd.

SUBMITTER: Galban CJ

PROVIDER: S-EPMC4947029 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Diffusion MRI in early cancer therapeutic response assessment.

Galbán C J CJ Hoff B A BA Chenevert T L TL Ross B D BD

NMR in biomedicine 20160115 3

Imaging biomarkers for the predictive assessment of treatment response in patients with cancer earlier than standard tumor volumetric metrics would provide new opportunities to individualize therapy. Diffusion-weighted MRI (DW-MRI), highly sensitive to microenvironmental alterations at the cellular level, has been evaluated extensively as a technique for the generation of quantitative and early imaging biomarkers of therapeutic response and clinical outcome. First demonstrated in a rodent tumor ...[more]

PMID: 26773848

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Project description:Background Whole-body diffusion-weighted (DW) MRI can help detect cancer with high sensitivity. However, the assessment of therapy response often requires information about tumor metabolism, which is measured with fluorine 18 fluorodeoxyglucose (FDG) PET. Purpose To compare tumor therapy response with whole-body DW MRI and FDG PET/MRI in children and young adults. Materials and Methods In this prospective, nonrandomized multicenter study, 56 children and young adults (31 male and 25 female participants; mean age, 15 years ± 4 [standard deviation]; age range, 6-22 years) with lymphoma or sarcoma underwent 112 simultaneous whole-body DW MRI and FDG PET/MRI between June 2015 and December 2018 before and after induction chemotherapy (ClinicalTrials.gov identifier: NCT01542879). The authors measured minimum tumor apparent diffusion coefficients (ADCs) and maximum standardized uptake value (SUV) of up to six target lesions and assessed therapy response after induction chemotherapy according to the Lugano classification or PET Response Criteria in Solid Tumors. The authors evaluated agreements between whole-body DW MRI- and FDG PET/MRI-based response classifications with Krippendorff α statistics. Differences in minimum ADC and maximum SUV between responders and nonresponders and comparison of timing for discordant and concordant response assessments after induction chemotherapy were evaluated with the Wilcoxon test. Results Good agreement existed between treatment response assessments after induction chemotherapy with whole-body DW MRI and FDG PET/MRI (α = 0.88). Clinical response prediction according to maximum SUV (area under the receiver operating characteristic curve = 100%; 95% confidence interval [CI]: 99%, 100%) and minimum ADC (area under the receiver operating characteristic curve = 98%; 95% CI: 94%, 100%) were similar (P = .37). Sensitivity and specificity were 96% (54 of 56 participants; 95% CI: 86%, 99%) and 100% (56 of 56 participants; 95% CI: 54%, 100%), respectively, for DW MRI and 100% (56 of 56 participants; 95% CI: 93%, 100%) and 100% (56 of 56 participants; 95% CI: 54%, 100%) for FDG PET/MRI. In eight of 56 patients who underwent imaging after induction chemotherapy in the early posttreatment phase, chemotherapy-induced changes in tumor metabolism preceded changes in proton diffusion (P = .002). Conclusion Whole-body diffusion-weighted MRI showed significant agreement with fluorine 18 fluorodeoxyglucose PET/MRI for treatment response assessment in children and young adults. © RSNA, 2020 Online supplemental material is available for this article.

Project description:Objective:To correlate changes in the apparent diffusion coefficient (ADC) from diffusion-weighted (DW)-MRI and standardised uptake value (SUV) from fluorothymidine (18FLT)-PET/CT with histopathological estimates of response in patients with non-small cell lung cancer (NSCLC) treated with neoadjuvant chemotherapy and track longitudinal changes in these biomarkers in a multicentre, multivendor setting. Methods:14 patients with operable NSCLC recruited to a prospective, multicentre imaging trial (EORTC-1217) were treated with platinum-based neoadjuvant chemotherapy. 13 patients had DW-MRI and FLT-PET/CT at baseline (10 had both), 12 were re-imaged at Day 14 (eight dual-modality) and nine after completing chemotherapy, immediately before surgery (six dual-modality). Surgical specimens (haematoxylin-eosin and Ki67 stained) estimated the percentage of residual viable tumour/necrosis and proliferation index. Results:Despite the small numbers,significant findings were possible. ADCmedian increased (p < 0.001) and SUVmean decreased (p < 0.001) significantly between baseline and Day 14; changes between Day 14 and surgery were less marked. All responding tumours (>30% reduction in unidimensional measurement pre-surgery), showed an increase at Day 14 in ADC75th centile and reduction in total lesion proliferation (SUVmean x proliferative volume) greater than established measurement variability. Change in imaging biomarkers did not correlate with histological response (residual viable tumour, necrosis). Conclusion:Changes in ADC and FLT-SUV following neoadjuvant chemotherapy in NSCLC were measurable by Day 14 and preceded changes in unidimensional size but did not correlate with histopathological response. However, the magnitude of the changes and their utility in predicting (non-) response (tumour size/clinical outcome) remains to be established. Advances in knowledge:During treatment, ADC increase precedes size reductions, but does not reflect histopathological necrosis.

Project description:ObjectivesTo assess the feasibility of the mono-exponential, bi-exponential and stretched-exponential models in evaluating response of breast tumours to neoadjuvant chemotherapy (NACT) at 3 T.MethodsThirty-six female patients (median age 53, range 32-75 years) with invasive breast cancer undergoing NACT were enrolled for diffusion-weighted MRI (DW-MRI) prior to the start of treatment. For assessment of early response, changes in parameters were evaluated on mid-treatment MRI in 22 patients. DW-MRI was performed using eight b values (0, 30, 60, 90, 120, 300, 600, 900 s/mm2). Apparent diffusion coefficient (ADC), tissue diffusion coefficient (D t), vascular fraction (ƒ), distributed diffusion coefficient (DDC) and alpha (α) parameters were derived. Then t tests compared the baseline and changes in parameters between response groups. Repeatability was assessed at inter- and intraobserver levels.ResultsAll patients underwent baseline MRI whereas 22 lesions were available at mid-treatment. At pretreatment, mean diffusion coefficients demonstrated significant differences between groups (p < 0.05). At mid-treatment, percentage increase in ADC and DDC showed significant differences between responders (49 % and 43 %) and non-responders (21 % and 32 %) (p = 0.03, p = 0.04). Overall, stretched-exponential parameters showed excellent repeatability.ConclusionDW-MRI is sensitive to baseline and early treatment changes in breast cancer using non-mono-exponential models, and the stretched-exponential model can potentially monitor such changes.Key points• Baseline diffusion coefficients demonstrated significant differences between complete pathological responders and non-responders. • Increase in ADC and DDC at mid-treatment can discriminate responders and non-responders. • The ƒ fraction at mid-treatment decreased in responders whereas increased in non-responders. • The mono- and stretched-exponential models showed excellent inter- and intrarater repeatability. • Treatment effects can potentially be assessed by non-mono-exponential diffusion models.

Project description:The aim of the study was to investigate dynamic contrast enhanced MRI (DCE-MRI) as a potential marker to assess the therapeutic responses of fecal microbiota transplantation (FMT) in patients with Crohn's disease (CD) and to determine the parameter or combination of parameters most strongly associated with changes in clinical indicators after treatment.In 22 CD patients, DCE-MRI was performed with a 3.0T scanner. Parameters of DCE-MRI (vascular transfer constant [K] and blood volume [BV]) in the terminal ileum were compared between before and day 90 after FMT treatment. The differences of clinical indicators (C-reactive protein [CRP], Harvey-Bradshaw index [HBI]) and DCE-MRI parameters (K, BV) between pre- and post-treatment was calculated by Student's 2-tailed, paired t-test. The correlations between percent change of clinical indicators (ΔCRP, ΔHBI) with DCE-MRI parameters (ΔK, ΔBV) were analyzed by Pearson's correlation coefficients. A logistic regression model was used to identify the changes of DCE-MRI parameters related to the treatment outcomes. Receiver operating characteristic curves (ROCs) were generated to assess which DCE-MRI parameter showed the best accuracy for evaluation of therapeutic response.After treatment, mean values of clinical indicators decreased significantly (CRP: 62.68 ± 31.86 vs 43.55 ± 29.63 mg/L, P = .008; HBI: 7.18 ± 2.10 vs 5.73 ± 2.33, P = 0.012). Both DCE-MRI parameters showed prominent differences before and after treatment: K (1.86 ± 0.87 vs 1.39 ± 0.83 min, P = .017), BV (61.02 ± 28.49 vs 41.96 ± 22.75 mL/100 g, P = .005). There were significant correlations between ΔCRP or ΔHBI and percent change of CDE-MRI parameters (ΔK to ΔCRP: 0.659; ΔK to ΔHBI: 0.496; ΔBV to ΔCRP: 0.442; ΔBV to ΔHBI: 0.476). Compared to ΔK and ΔBV individually, the combination of both parameters performed best in assessment of therapeutic response with an area under the ROCs (AUC) of 0.948.K and BV parameters derived from DCE-MRI have the potential to assess for therapeutic response after FMT treatment for CD. The combination of K and BV measurements improved the predictive capability compared to the individual parameters.

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Diffusion MRI in early cancer therapeutic response assessment.

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Diffusion MRI in early cancer therapeutic response assessment.

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