Addition of epidermal growth factor receptor inhibitors to standard chemotherapy increases survival of advanced head and neck squamous cell carcinoma patients: A systematic review and meta-analysis.

Head and neck squamous cell carcinoma (HNSCC) is among the common tumors associated with high mortality. The aim of our meta-analysis was to determine how additional anti-epidermal growth factor receptor (EGFR) therapy to standard chemotherapy affects the progression-free (PFS) and overall survival (OS) of the patients, besides the most common side effects. We used CENTRAL, MEDLINE, and Embase databases until October 26, 2020, and included 13 eligible randomized controlled trials in our systematic research. The pooled hazard ratios (HR) for the main outcomes from the original data were estimated and for the other dichotomous outcomes, odds ratios (ORs) with their 95% confidence intervals (CI) were calculated. Addition of EGFR inhibitors to conventional chemotherapy significantly decreased the death and disease progression (for PFS HR: 0.68, 95% CI: 0.55-0.81, I2  = 65.5%, p = 0.005) and mortality (for OS HR: 0.83, 95% CI: 0.72-0.94, I2  = 42.3%, p = 0.076). In the EGFR inhibitor group, we revealed an increased chance of the over Grade 3 skin rashes (OR: 4.86; 95% CI: 1.52-15.49, I2  = 2.3%, p = 0.407), and all Grade skin rashes (OR: 18.32, 95% CI: 8.07-41.60, I2  = 56.6%, p = 0.032). Despite their unwanted dermatological side effects, the addition of EGFR inhibitors is recommended to be included in advanced HNSCC therapy.

Differences in the serum metabolome and lipidome identify potential biomarkers for seronegative rheumatoid arthritis versus psoriatic arthritis.

OBJECTIVES: The differential diagnosis of seronegative rheumatoid arthritis (negRA) and psoriasis arthritis (PsA) is often difficult due to the similarity of symptoms and the unavailability of reliable clinical markers. Since chronic inflammation induces major changes in the serum metabolome and lipidome, we tested whether differences in serum metabolites and lipids could aid in improving the differential diagnosis of these diseases. METHODS: Sera from negRA and PsA patients with established diagnosis were collected to build a biomarker-discovery cohort and a blinded validation cohort. Samples were analysed by proton nuclear magnetic resonance. Metabolite concentrations were calculated from the spectra and used to select the variables to build a multivariate diagnostic model. RESULTS: Univariate analysis demonstrated differences in serological concentrations of amino acids: alanine, threonine, leucine, phenylalanine and valine; organic compounds: acetate, creatine, lactate and choline; and lipid ratios L3/L1, L5/L1 and L6/L1, but yielded area under the curve (AUC) values lower than 70%, indicating poor specificity and sensitivity. A multivariate diagnostic model that included age, gender, the concentrations of alanine, succinate and creatine phosphate and the lipid ratios L2/L1, L5/L1 and L6/L1 improved the sensitivity and specificity of the diagnosis with an AUC of 84.5%. Using this biomarker model, 71% of patients from a blinded validation cohort were correctly classified. CONCLUSIONS: PsA and negRA have distinct serum metabolomic and lipidomic signatures that can be used as biomarkers to discriminate between them. After validation in larger multiethnic cohorts this diagnostic model may become a valuable tool for a definite diagnosis of negRA or PsA patients.

Integrating functional MRI information into conventional 3D radiotherapy planning of CNS tumors. Is it worth it?

The purpose of our study was to examine the potential benefits of integrating functional MRI (fMRI) information into the 3D-based planning process for central nervous system (CNS) malignancies. Between 01.01.2008 and 01.12.2009, ten patients with astrocytoma (both low and high-grade histological type) were enrolled in this study. Before the planning process, conventional CT planning, postoperative MR, and individual functional MRI examinations were conducted. For the functional MRI examination four types of conventional stimuli were applied: acoustic, visual, somatosensory, and numeric. To examine the potential benefits of using fMRI-based information, three different types of theoretical planning were applied and compared: 3D conformal plan without fMRI information, 3D conformal plan with fMRI information, and IMRT plan with fMRI information. DVH analysis and the NTCP model were used for plan comparison. When comparing planning methods, distance-related subgroups were generated and studied. By using the additional fMRI information, a significantly higher sparing effect can be achieved on these ORs (both with conventional 3D-based planning and IMRT). In cases when the OR-PTV distance is less than 1 cm, IMRT seems to be a significantly better choice than conventional 3D-based techniques. IMRT also has an additional sparing effect on the optic tract and brainstem, especially for locations close to the midline. Our results demonstrated that using fMRI information in conventional 3D-based treatment planning has the potential benefit of significant dose reduction for the critical organs, with no compromise in PTV coverage even when using conventional 3D planning. fMRI can be widely used in low-grade cases (long life expectancy, lower acute and late toxicity) and also in cases with high-grade astrocytomas or distant metastases (higher dose to PTV with better sparing of risk organs). In cases when the OR-PTV distance is less than 1 cm, IMRT should be the choice of treatment for a higher sparing effect on functional active areas. Longer imaging and clinical follow up are needed to confirm the real sparing effect on these functional areas.

Integrating functional MRI information into radiotherapy planning of CNS tumors-early experiences.

The purpose of our study was to examine the integration of functional MRI (fMRI) information into 3D based planning process of the central nervous system (CNS) malignancies. Between 01.01.2008 and 01.12.2008 four patients with astrocytoma were enrolled to this study. Before the planning process conventional planning CT, postoperative MR and individual functional MRI examinations were delivered. For the functional MRI examination the following four types of stimulus were applied: acoustic, visual, somatosensory and numeral. Three different theoretical planning situations were applied and compared: 3D conformal plan without fMRI information, 3D conformal plan with fMRI information and IMRT plan with fMRI information. For plan comparison DVH analysis, and NTCP model were used. fMRI based OR definition resulted in 4 additional OR's in the contouring process. As these cases demonstrate, an average of 50% dose reduction was achieved in OR, OR2 and OR3 with IMRT and fMRI based 3D planning, especially in case of midline localization and big tumor extent. IMRT provides additional sparing effect in the optic tract and brainstem, especially for localizations close to the midline. Our results demonstrated that using fMRI information in conventional 3D based treatment planning potentially benefits significant dose reduction in critical organs, with no compromise in PTV coverage. fMRI can be widely used even in low grade cases (long life expectancies, lower acute and late toxicity in radiotherapy) and in cases with high grade astrocytomas or metastases (higher dose to PTV with better risk organ sparing in radiotherapy).