Epilepsy in children is the most frequent, heterogeneous and difficult to classify chronic neurologic condition with the etiology found in 35–40% of patients. Our aim is to detect the metabolic differences between the epileptic children and the children with no neurological abnormalities in order to define the metabolic background for therapy monitoring. The studied group included 28 epilepsy patients (median age 12 months) examined with a diagnostic protocol including EEG, videoEEG, 24-hour-EEG, tests for inborn errors of metabolism, chromosomal analysis and molecular study. The reference group consisted of 20 patients (median age 20 months) with no neurological symptoms, no development delay nor chronic diseases. ¹H-NMR serum spectra were acquired on 400 MHz spectrometer and analyzed using multivariate and univariate approach with the application of correction for age variation. The epilepsy group was characterized by increased levels of serum N-acetyl-glycoproteins, lactate, creatine, glycine and lipids, whereas the levels of citrate were decreased as compared to the reference group. Choline, lactate, formate and dimethylsulfone were significantly correlated with age. NMR-based metabolomics could provide information on the dynamic metabolic processes in drug-resistant epilepsy yielding not only disease-specific biomarkers but also profound insights into the disease course, treatment effects or drug toxicity.

Introduction Nutritional treatment in head and neck squamous cell carcinoma cancer (HNSCC) patients undergoing radio-/chemo-radiotherapy (RT/CHRT) is complex and requires a multidisciplinary approach. In this study the real-time dynamic changes in serum metabolome during RT/CHRT in HNSCC patients were monitored using NMR-based metabolomics. Objectives The main goal was to find the metabolic markers that could help prevent of acute radiation sequelae (ARS) escalation. Methods 170 HNSCC patients were treated radically with RT/CHRT. Blood samples were collected weekly, starting from the day before the treatment and stopping within the week after the RT/CHRT completion, resulting in a total number of 1328 samples. ¹H NMR spectra were acquired on Bruker 400 MHz spectrometer at 310 K and analyzed using principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). Additional statistical analyses were performed on the quantified metabolites. Results PCA has detected a group of distinct outliers corresponding to ketone bodies (3HB, Ace, AceAce). These outliers were found to identify the individuals at high risk of weight loss, mainly by the 3HB changes, which was confirmed by the patients’ medical data. In the OPLS-DA models a transition from the lowest to the highest weight loss is seen, defining the metabolic time trajectories for the patients from the studied groups during RT/CHRT. 3HB is a relatively sensitive marker that allows earlier identification of the patients at higher risk of > 10% weight loss. Conclusion Our findings indicate that metabolic alterations, characteristic for malnutrition or cachexia, can be detected already at the beginning of the treatment, making it possible to monitor the patients with a higher risk of weight loss.

This review focuses on the molecular biology of head and neck squamous cell carcinomas and presents current and emerging biomarkers of the response of patients to induction chemotherapy. The usefulness of genes, proteins, and parameters from diagnostic clinical imaging as well as other clinicopathological parameters is thoroughly discussed. The role of induction chemotherapy before radiotherapy or before chemo-radiotherapy is still debated, as the data on its efficacy are somehow confusing. Despite the constant improvement of treatment protocols and the introduction of new cytostatics, there is still no consensus regarding the use of induction chemotherapy in the treatment of head and neck cancer, with the possible exception of larynx preservation. Such difficulties indicate that potential future treatment strategies should be personalized. Personalized medicine, in which individual tumor genetics drive the selection of targeted therapies and treatment plans for each patient, has recently emerged as the next generation of cancer therapy. Early prediction of treatment outcome or its toxicity may be highly beneficial for those who are at risk of the development of severe toxicities or treatment failure—a different treatment strategy may be applied to these patients, sparing them unnecessary pain. The literature search was carried out in the PubMed and ScienceDirect databases as well as in the selected conference proceedings repositories. Of the 265 articles and abstracts found, only 30 met the following inclusion criteria: human studies, analyzing prediction of induction chemotherapy outcome or toxicity based on the pretreatment (or after the first cycle, if more cycles of induction were administered) data, published after the year 2015. The studies regarding metastatic and recurrent cancers as well as the prognosis of overall survival or the outcome of consecutive treatment were not taken into consideration. As revealed from the systematic inspection of the papers, there are over 100 independent parameters analyzed for their suitability as prognostic markers in HNSCC patients undergoing induction chemotherapy. Some of them are promising, but usually they lack important features such as high specificity and sensitivity, low cost, high positive predictive value, clinical relevance, short turnaround time, etc. Subsequent studies are necessary to confirm the usability of the biomarkers for personal medicine.

In the present study, we analyze the nuclear magnetic resonance (NMR) blood serum metabolic profiles of 106 head and neck squamous cell carcinoma (HNSCC) patients during radio (RT) and concurrent radio-chemotherapy (CHRT). Four different fractionation schemes were compared. The blood samples were collected weekly, from the day before the treatment until the last week of CHRT/RT. The NMR spectra were acquired on A Bruker 400 MHz spectrometer at 310 K and analyzed using multivariate methods. Seven metabolites were found significantly to be altered solely by radiotherapy: N-acetyl-glycoprotein (NAG), N-acetylcysteine, glycerol, glycolate and the lipids at 0.9, 1.3 and 3.2 ppm. The NMR results were correlated with the tissue volumes receiving a particular dose of radiation. The influence of the irradiated volume on the metabolic profile is weak and mainly limited to sparse correlations with the inflammatory markers, creatinine and the lymphocyte count in RT and the branched-chain amino-acids in CHRT. This is probably due to the optimal planning and delivery of radiotherapy improving sparing of the surrounding normal tissues and minimizing the differences between the patients (caused by the tumor location and size).

Background: The aim of this prospective study is to identify the biomarkers associated with the effects of induction chemotherapy (iCHT) in terms of the favorable/weaker response to the treatment in locally advanced head and neck squamous cells carcinomas (LA-HNSCC). Methods: The studied group consisted of 53 LA-HNSCC patients treated with iCHT. The treatment tolerance was measured by the Common Terminology Criteria for Adverse Events (CTCAE). The response to the treatment was evaluated by the clinical, fiberoptic and radiological examinations made before and after iCHT (the TNM Classification of Malignant Tumors was used for classifying the extent of cancer spread). Proton nuclear magnetic resonance (¹H NMR) serum spectra of the samples collected before and after iCHT were acquired with a 400 MHz spectrometer and analyzed using the multivariate and univariate statistical methods. Results: The molecular response to iCHT involves an increase of the serum lipids which is accompanied by the simultaneous decrease of alanine, glucose and N-acetyl-glycoprotein (NAG). Furthermore, in males, the iCHT induced changes in the lipid signals and NAG significantly correlate with the regression of the primary tumor. The OPLS-DA multivariate model identified two subgroups of the patients with a weaker metabolic and clinical response. The first one consisted of the patients with a significantly lower initial nodal stage, the second one showed no differences in the initial clinical and metabolic statuses. Conclusions: The NMR-based metabolomic study of the serum spectra revealed that iCHT induces the marked changes in the LA-HNSCC patients’ metabolic profiles and makes it possible to stratify the patients according to their response to iCHT. These effects are sex dependent. Further studies on a larger scale accounting for sex and the clinical and metabolic factors are warranted.