Abstract
BackgroundGlioblastomas progress rapidly making response evaluation using MRI insufficient since treatment effects are not detectable until months after initiation of treatment. Thus, there is a strong need for supplementary biomarkers that could provide reliable and early assessment of treatment efficacy. Analysis of alterations in the metabolome may be a source for identification of new biomarker patterns harboring predictive information. Ideally, the biomarkers should be found within an easily accessible compartment such as the blood.MethodUsing gas-chromatographic- time-of-flight-mass spectroscopy we have analyzed serum samples from 11 patients with glioblastoma during the initial phase of radiotherapy. Fasting serum samples were collected at admittance, on the same day as, but before first treatment and in the morning after the second and fifth dose of radiation. The acquired data was analyzed and evaluated by chemometrics based bioinformatics methods. Our findings were compared and discussed in relation to previous data from microdialysis in tumor tissue, i.e. the extracellular compartment, from the same patients.ResultsWe found a significant change in metabolite pattern in serum comparing samples taken before radiotherapy to samples taken during early radiotherapy. In all, 68 metabolites were lowered in concentration following treatment while 16 metabolites were elevated in concentration. All detected and identified amino acids and fatty acids together with myo-inositol, creatinine, and urea were among the metabolites that decreased in concentration during treatment, while citric acid was among the metabolites that increased in concentration. Furthermore, when comparing results from the serum analysis with findings in tumor extracellular fluid we found a common change in metabolite patterns in both compartments on an individual patient level. On an individual metabolite level similar changes in ornithine, tyrosine and urea were detected. However, in serum, glutamine and glutamate were lowered after treatment while being elevated in the tumor extracellular fluid.ConclusionCross-validated multivariate statistical models verified that the serum metabolome was significantly changed in relation to radiation in a similar pattern to earlier findings in tumor tissue. However, all individual changes in tissue did not translate into changes in serum. Our study indicates that serum metabolomics could be of value to investigate as a potential marker for assessing early response to radiotherapy in malignant glioma.Electronic supplementary materialThe online version of this article (doi:10.1186/s13014-016-0626-6) contains supplementary material, which is available to authorized users.
Highlights
Glioblastomas progress rapidly making response evaluation using MRI insufficient since treatment effects are not detectable until months after initiation of treatment
All detected and identified amino acids and fatty acids together with myo-inositol, creatinine, and urea were among the metabolites that decreased in concentration during treatment, while citric acid was among the metabolites that increased in concentration
Our study indicates that serum metabolomics could be of value to investigate as a potential marker for assessing early response to radiotherapy in malignant glioma
Summary
Glioblastomas progress rapidly making response evaluation using MRI insufficient since treatment effects are not detectable until months after initiation of treatment. There is a strong need for supplementary biomarkers that could provide reliable and early assessment of treatment efficacy. Today the standard treatment is based on surgery followed by radiochemotherapy and adjuvant temozolomide When these measures fail, surgery may be considered as well as second line chemotherapy and reirradiation in selected cases. The tumors are fast growing and response evaluation with repeated CT or MRI is not sufficient since morphological changes in many cases are detected too late to influence treatment strategies. There is an obvious need for markers that could provide a reliable and early assessment of treatment efficacy. In a recent report it was found that metabolic changes reflecting tumor progression may appear earlier than morphological alteration as assessed with MRI [2]. In a recent review, Nelson stressed the insufficiency of morphology assessment and called for utilizing metabolic and physiological MR methods to assess therapeutic response [3]
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