Functional Diffusion Map As an Early Imaging Biomarker for High-Grade Glioma: Correlation With Conventional Radiologic Response and Overall Survival

University of Michigan, Ann Arbor, Michigan, United States
Journal of Clinical Oncology (Impact Factor: 18.43). 08/2008; 26(20):3387-94. DOI: 10.1200/JCO.2007.15.2363
Source: PubMed


Assessment of radiologic response (RR) for brain tumors utilizes the Macdonald criteria 8 to 10 weeks from the start of treatment. Diffusion magnetic resonance imaging (MRI) using a functional diffusion map (fDM) may provide an earlier measure to predict patient survival.
Sixty patients with high-grade glioma were enrolled onto a study of intratreatment MRI at 1, 3, and 10 weeks. Receiver operating characteristic curve analysis was used to evaluate imaging parameters as a function of patient survival at 1 year. Both log-rank and Cox proportional hazards models were utilized to assess overall survival.
Greater increases in diffusion in response to therapy over time were observed in those patients alive at 1 year compared with those who died as a result of disease. The volume of tumor with increased diffusion by fDM at 3 weeks was the strongest predictor of patient survival at 1 year, with larger fDM predicting longer median survival (52.6 v 10.9 months; log-rank, P < .003; hazard ratio [HR] = 2.7; 95% CI, 1.5 to 5.9). Radiologic response at 10 weeks had similar prognostic value (median survival, 31.6 v 10.9 months; log-rank P < .0007; HR = 2.9; 95% CI, 1.7 to 7.2). Radiologic response and fDM differed in 25% of cases. A composite index of response including fDM and RR provided a robust predictor of patient survival and may identify patients in whom RR does not correlate with clinical outcome.
Compared with conventional neuroimaging, fDM provided an earlier assessment of equal predictive value, and the combination of fDM and RR provided a more accurate prediction of patient survival than either metric alone.

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Available from: Daniel A Hamstra, Sep 08, 2014
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    • "These include the evaluation of histograms of ADC at single time points [20] [21] and the functional diffusion map (fDM), which describes changes between ADC values on a pixel-by-pixel basis in overlapping regions of the CEL from two successive scans [17] [18]. Although these methods have been applied to the assessment of agents such as bevacizumab [19] [22], the relatively small size of the CEL in follow-up scans means that they do not meet the cutoff criterion of 3 to 4 cm 3 that was originally defined for this type of analysis [17] [18]. "
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    ABSTRACT: Purpose: To evaluate the time course and association with survival of anatomic lesion volumes and diffusion imaging parameters for patients with newly diagnosed glioblastoma who were treated with radiation and concurrently with either temozolomide and enzastaurin (TMZ+enza cohort) or temozolomide, erlotonib, and bevaciumab (TMZ+erl+bev cohort). Materials and methods: Regions of interest corresponding to the contrast-enhancing and hyperintense lesions on T2-weighted images were generated. Diffusion-weighted images were processed to provide maps of apparent diffusion coefficient, fractional anisotropy, and longitudinal and radial eigenvalues. Histograms of diffusion values were generated and summary statistics calculated. Cox proportional hazards models were employed to assess the association of representative imaging parameters with survival with adjustments for age, Karnofsky performance status, and extent of resection. Results: Although progression-free survival was significantly longer for the TMZ+erl+bev cohort (12.8 vs 7.3 months), there was no significant difference in overall survival between the two populations (17.0 vs 17.8 months). The median contrast-enhancing lesion volumes decreased from 6.3 to 1.9 cm(3) from baseline to the postradiotherapy scan for patients in the TMZ+enza cohort and from 2.8 to 0.9cm(3) for the TMZ+erl+bev cohort. Changes in the T2 lesion volumes were only significant for the latter cohort (26.5 to 11.9 cm(3)). The median apparent diffusion coefficient and related diffusion parameters were significantly increased for the TMZ+enza cohort (1054 to 1225 μm(2)/s). More of the anatomic parameters were associated with survival for the TMZ+enza cohort, whereas more diffusion parameters were associated with survival for the TMZ+erl+bev cohort. Conclusion: The early changes in anatomic and diffusion imaging parameters and their association with survival reflected differences in the mechanisms of action of the treatments that were being given. This suggests that integrating diffusion metrics and anatomic lesion volumes into the Response Assessment in Neuro-Oncology criteria would assist in interpreting treatment-induced changes and predicting outcome in patients with newly diagnosed glioblastoma who are receiving such combination treatments.
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    • "Acquisition sequences for DWI are not completely standardized, but basic techniques are well known and available on systems from all major vendors. There is no established standard for measurement of ADC but recent reports promote voxel-based analysis and volumetric evaluation of ADC (vADC) which is well correlated with cellularity, as shown in gliomas [27,28]. This method also carries the advantages of being less operator-dependent and more reproducible than ROI-based techniques. "
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    ABSTRACT: Background: Metastatic colorectal cancer (mCRC) may present various behaviours that define different courses of tumor evolution. There is presently no available tool designed to assess tumor aggressiveness, despite the fact that this is considered to have a major impact on patient outcome. Methods/design: CORIOLAN is a single-arm prospective interventional non-therapeutic study aiming mainly to assess the natural tumor metabolic progression index (TMPI) measured by serial FDG PET-CT without any intercurrent antitumor therapy as a prognostic factor for overall survival (OS) in patients with mCRC.Secondary objectives of the study aim to test the TMPI as a prognostic marker for progression-free survival (PFS), to assess the prognostic value of baseline tumor FDG uptake on PFS and OS, to compare TMPI to classical clinico-biological assessment of prognosis, and to test the prognostic value on OS and PFS of MRI-based apparent diffusion coefficient (ADC) and variation of vADC using voxel-based diffusion maps.Additionally, this study intends to identify genomic and epigenetic factors that correlate with progression of tumors and the OS of patients with mCRC. Consequently, this analysis will provide information about the signaling pathways that determine the natural and therapy-free course of the disease. Finally, it would be of great interest to investigate whether in a population of patients with mCRC, for which at present no known effective therapy is available, tumor aggressiveness is related to elevated levels of circulating tumor cells (CTCs) and to patient outcome. Discussion: Tumor aggressiveness is one of the major determinants of patient outcome in advanced disease. Despite its importance, supported by findings reported in the literature of extreme outcomes for patients with mCRC treated with chemotherapy, no objective tool allows clinicians to base treatment decisions on this factor. The CORIOLAN study will characterize TMPI using FDG-PET-based metabolic imaging of patients with chemorefractory mCRC during a period of time without treatment. Results will be correlated to other assessment tools like DW-MRI, CTCs and circulating DNA, with the aim to provide usable tools in daily practice and in clinical studies in the future. Clinical trialsgov number: NCT01591590.
    Full-text · Article · May 2014 · BMC Cancer
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    • "Determining treatment response early on in the treatment cycle is of vital importance for moving toward personalized medicine with the ability to alter doses or change therapy in those cases where the current treatment is seen to be ineffective. The fDM was previously shown to be an effective biomarker for detecting treatment response earlier than current standard techniques that consist of radiological assessment, in most cases at the end of therapy.13 However, in this analysis, a number of limitations have been identified and studied, which indicates the need to exercise caution when interpreting fDM results. "
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    ABSTRACT: Background The functional diffusion map (fDM) has been suggested as a tool for early detection of tumor treatment efficacy. We aim to study 3 factors that could act as potential confounders in the fDM: areas of necrosis, tumor grade, and change in tumor size.Methods Thirty-four pediatric patients with brain tumors were enrolled in a retrospective study, approved by the local ethics committee, to examine the fDM. Tumors were selected to encompass a range of types and grades. A qualitative analysis was carried out to compare how fDM findings may be affected by each of the 3 confounders by comparing fDM findings to clinical image reports.ResultsResults show that the fDM in areas of necrosis do not discriminate between treatment response and tumor progression. Furthermore, tumor grade alters the behavior of the fDM: a decrease in apparent diffusion coefficient (ADC) is a sign of tumor progression in high-grade tumors and treatment response in low-grade tumors. Our results also suggest using only tumor area overlap between the 2 time points analyzed for the fDM in tumors of varying size.Conclusions Interpretation of fDM results needs to take into account the underlying biology of both tumor and healthy tissue. Careful interpretation of the results is required with due consideration to areas of necrosis, tumor grade, and change in tumor size.
    Full-text · Article · Dec 2013 · Neuro-Oncology
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