Association of early changes in<sup>1</sup>H MRSI parameters with survival for patients with newly diagnosed glioblastoma receiving a multimodality treatment regimen

Nelson, Sarah J.; Kadambi, A.; Park, Ilwoo; Li, Yan; Crane, Jason C.; Olson, Marram P.; Molinaro, Annette M.; Roy, Ritu; Butowski, Nicholas; Cha, Soonmee; Chang, Susan M.

doi:10.1093/neuonc/now159

Cited by 23 publications

(29 citation statements)

References 33 publications

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“…In a small cohort only biomarkers that show a large effect size can be tested, multivariate analysis is limited to few variables, and the sampling bias cannot be excluded. However, recent studies 36 , 37 performed with more subjects support the value of MRSI to monitor treatment response in GBM patients. Taken together, our study and others advocate for an earlier imaging investigation time point around the middle of radiotherapy period in GBM.…”

Section: Discussionmentioning

confidence: 99%

Early changes in glioblastoma metabolism measured by MR spectroscopic imaging during combination of anti-angiogenic cediranib and chemoradiation therapy are associated with survival

et al. 2017

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Precise assessment of treatment response in glioblastoma during combined anti-angiogenic and chemoradiation remains a challenge. In particular, early detection of treatment response by standard anatomical imaging is confounded by pseudo-response or pseudo-progression. Metabolic changes may be more specific for tumor physiology and less confounded by changes in blood–brain barrier permeability. We hypothesize that metabolic changes probed by magnetic resonance spectroscopic imaging can stratify patient response early during combination therapy. We performed a prospective longitudinal imaging study in newly diagnosed glioblastoma patients enrolled in a phase II clinical trial of the pan-vascular endothelial growth factor receptor inhibitor cediranib in combination with standard fractionated radiation and temozolomide (chemoradiation). Forty patients were imaged weekly during therapy with an imaging protocol that included magnetic resonance spectroscopic imaging, perfusion magnetic resonance imaging, and anatomical magnetic resonance imaging. Data were analyzed using receiver operator characteristics, Cox proportional hazards model, and Kaplan–Meier survival plots. We observed that the ratio of total choline to healthy creatine after 1 month of treatment was significantly associated with overall survival, and provided as single parameter: (1) the largest area under curve (0.859) in receiver operator characteristics, (2) the highest hazard ratio (HR = 85.85, P = 0.006) in Cox proportional hazards model, (3) the largest separation (P = 0.004) in Kaplan–Meier survival plots. An inverse correlation was observed between total choline/healthy creatine and cerebral blood flow, but no significant relation to tumor volumetrics was identified. Our results suggest that in vivo metabolic biomarkers obtained by magnetic resonance spectroscopic imaging may be an early indicator of response to anti-angiogenic therapy combined with standard chemoradiation in newly diagnosed glioblastoma.

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Section: Discussionmentioning

confidence: 99%

Early changes in glioblastoma metabolism measured by MR spectroscopic imaging during combination of anti-angiogenic cediranib and chemoradiation therapy are associated with survival

et al. 2017

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“…Potential applications of automated lesion delineation from MRSI include longitudinal measurements to monitor treatment and for definition of radiation treatment volumes. The clinical potential for these measurements remains to be evaluated; however, initial studies that have been carried out for image-guided resection, 10 radiation treatment, 12 and treatment response assessment 11,29 indicate considerable benefit from incorporating the MRSI information. A limitation for more widespread use for clinical studies remains the quality F I G U R E 8 Example Cho/NAA map and segmentation results for a grade III glioma that includes two regions with differing intensity of the Cho/NAA map.…”

Section: Discussionmentioning

confidence: 99%

Lesion segmentation for MR spectroscopic imaging using the convolution difference method

Maudsley

2018

Magnetic Resonance in Med

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Purpose Delineation of lesion boundaries from volumetric MRSI metabolite ratio maps using a method that accounts for the spatial response function of the acquisition and variable spectral quality and is robust to signal heterogeneity within the lesion. Methods A novel method for lesion segmentation, termed convolution difference, has been developed that is robust to signal heterogeneity within the lesion and to differences in the spatial response function. Procedures are described for processing metabolite ratio maps and to exclude regions of inadequate spectral quality. This method was evaluated using computer simulations, and the results were compared with an iterative thresholding technique that determines an optimal amplitude threshold, and with the use of a fixed amplitude threshold. These methods were evaluated for segmentation of volumetric MRSI studies of gliomas using maps of the choline to N–acetylaspartate ratio, and a qualitative comparison of lesion volumes carried out. Results Simulation studies indicated improved performance for the convolution difference method when applied to ratio maps. Variations in tumor volume were observed for the in vivo studies between the convolution difference and the iterative thresholding methods; however, visual analysis indicates that both showed improved accuracy in comparison to using a fixed amplitude threshold. Conclusion This study reinforces previous reports indicating that the use of fixed threshold values for segmentation of maps with broad spatial response functions can result in errors in lesion volume definition. A novel segmentation method, termed the convolution difference, has been introduced and demonstrated to be robust for segmentation of volumetric MRSI metabolite data.

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“…These ‘metabolic abnormality regions’ have been shown to extend beyond structural MRI‐defined abnormality boundaries . This is helping to better define resection margins, radiosurgery limits and malignant transformation in recurrent glioma, as well as to associate CNI metrics to survival after various therapeutic protocols, and to identify tumour regions at risk for progression Take‐home message .…”

Section: Mrs(i)‐detectable Metabolic Hallmarks Of Cancer: Applicationmentioning

confidence: 99%

“…This uses 2D single slice data. However, MRSI might be a useful supplementary tool for this purpose allowing to monitor and follow‐up brain tumour molecular properties and heterogeneity for the whole tissue (3D). Most of the time, authors focus their analysis on a few metabolites or metabolite ratios (the CNI in brain tumours, the (Cho + PA + Cr)/Cit ratio in prostate cancers), neglecting the rest of the spectral pattern, as has been discussed in Section .…”

Section: Mrs Cancer Patternmentioning

confidence: 99%

“…Most of the time, authors focus their analysis on a few metabolites or metabolite ratios (the CNI in brain tumours, the (Cho + PA + Cr)/Cit ratio in prostate cancers), neglecting the rest of the spectral pattern, as has been discussed in Section . This has been evolving, and recently classic ‘single ratio’ groups have been considering additional metabolite‐derived metrics: edited Lac, Cho/NAA and lipid/NAA indexes …”

Section: Mrs Cancer Patternmentioning

confidence: 99%

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Cancer metabolism in a snapshot: MRS(I)

2019

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The contribution of MRS(I) to the in vivo evaluation of cancer-metabolism-derived metrics, mostly since 2016, is reviewed here. Increased carbon consumption by tumour cells, which are highly glycolytic, is now being sampled by 13 C magnetic resonance spectroscopic imaging (MRSI) following the injection of hyperpolarized [1-13 C] pyruvate (Pyr). Hot-spots of, mostly, increased lactate dehydrogenase activity or flow between Pyr and lactate (Lac) have been seen with cancer progression in prostate (preclinical and in humans), brain and pancreas (both preclinical) tumours. Therapy response is usually signalled by decreased Lac/Pyr 13 C-labelled ratio with respect to untreated or nonresponding tumour. For therapeutic agents inducing tumour hypoxia, the 13 C-labelled Lac/bicarbonate ratio may be a better metric than the Lac/Pyr ratio. 31 P MRSI may sample intracellular pH changes from brain tumours (acidification upon antiangiogenic treatment, basification at fast proliferation and relapse). The steady state tumour metabolome pattern is still in use for cancer evaluation. Metrics used for this range from quantification of single oncometabolites (such as 2-hydroxyglutarate in mutant IDH1 glial brain tumours) to selected metabolite ratios (such as total choline to N-acetylaspartate (plain ratio or CNI index)) or the whole 1 H MRSI(I) pattern through pattern recognition analysis. These approaches have been applied to address different questions such as tumour subtype definition, following/predicting the response to therapy or defining better resection or radiosurgery limits. KEYWORDSanimal model study, cancer, cellular and molecular cancer imaging, hyperpolarized C-13, MRS and MRSI methods, phosphorus MRS/MRSI | TEMPORAL AND THEMATIC BOUNDARIES OF THE TOPICS COVEREDThe authors of this review declare at the outset that there is no intention of being exhaustive or systematic. The temporal boundaries reviewed will be modest: only relevant literature since 2016, chosen according to our bias. Earlier work or reviews will only be referred to in order to put recent findings in due perspective. Authors hope that this summary will give readers a picture of how far cancer metabolism analysis with MRS(I) has advanced and, perhaps, why it is not advancing further.For quite a long time MRS, rather than MRI, has been the only approach able to evaluate cancer metabolism. Nevertheless, the MRI-derived information related to cancer metabolism should not be forgotten: consider for example the chemical exchange saturation transfer (CEST) effect caused by exchangeable protons in water-derived images of glucose uptake and metabolism in tumours. 1,2 However, apart from these CESTrelated studies, we should acknowledge that most information about cancer metabolism using MR still refers to MRS(I) acquisitions, which are the ones dealt with in our text.Supplementary Figure 1 shows a PUBMED search illustrating the different proportions of articles investigating several cancer types through MRS(I) approaches. The retrieved information can help unders...

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Association of early changes in¹H MRSI parameters with survival for patients with newly diagnosed glioblastoma receiving a multimodality treatment regimen

Cited by 23 publications

References 33 publications

Early changes in glioblastoma metabolism measured by MR spectroscopic imaging during combination of anti-angiogenic cediranib and chemoradiation therapy are associated with survival

Early changes in glioblastoma metabolism measured by MR spectroscopic imaging during combination of anti-angiogenic cediranib and chemoradiation therapy are associated with survival

Lesion segmentation for MR spectroscopic imaging using the convolution difference method

Cancer metabolism in a snapshot: MRS(I)

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Association of early changes in1H MRSI parameters with survival for patients with newly diagnosed glioblastoma receiving a multimodality treatment regimen

Cited by 23 publications

References 33 publications

Early changes in glioblastoma metabolism measured by MR spectroscopic imaging during combination of anti-angiogenic cediranib and chemoradiation therapy are associated with survival

Early changes in glioblastoma metabolism measured by MR spectroscopic imaging during combination of anti-angiogenic cediranib and chemoradiation therapy are associated with survival

Lesion segmentation for MR spectroscopic imaging using the convolution difference method

Cancer metabolism in a snapshot: MRS(I)

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Association of early changes in¹H MRSI parameters with survival for patients with newly diagnosed glioblastoma receiving a multimodality treatment regimen