Tumor lactate content predicts for response to fractionated irradiation of human squamous cell carcinomas in nude mice
Abstract Background and purpose The present study was performed to test the hypothesis that lactate accumulation correlates with the radioresistance of malignant tumors due to the radical scavenging capacity of lactate or metabolic intermediates of glycolysis, such as pyruvate. Materials and methods Five human head and neck squamous cell carcinoma cell lines (HNSCCs) xenografted in nude mice were treated with a clinically relevant irradiation protocol with 30 fractions within 6 weeks. The radiation dose necessary to locally control 50% of the tumors (TCD 50 ) ranged from 47.4 to 129.8Gy. Concentrations of glucose, lactate, and ATP in viable tumor regions as potential indicators of glycolyti…
MR Thermometry Data Correlate with Pathological Response for Soft Tissue Sarcoma of the Lower Extremity in a Single Center Analysis of Prospectively Registered Patients.
Background: There is a strong biologic rationale for using locoregional hyperthermia in soft tissue sarcoma and a randomized trial reported significant improvements with hyperthermia. The aim of this study was to describe the opportunities of magnetic resonance (MR)-based thermometry in a cohort of soft tissue sarcoma patients undergoing combined radiotherapy and locoregional hyperthermia. Patients and Methods: For eleven evaluable patients, tumor volume (VTu) and a separate volume for temperature analysis with reliable temperature distribution (Vtherm) were contoured for every hyperthermia treatment (103 therapies). Temperature data were recorded for all tumors and were correlated with cli…
Co-localisation of hypoxia and perfusion markers with parameters of glucose metabolism in human squamous cell carcinoma (hSCC) xenografts
Purpose: To examine relationships between tumour hypoxia, perfusion and metabolic microenvironment at themicroregional level in three different human squamous cell carcinomas (hSCC). Materials and methods: Nude mice bearing FaDu, UT-SCC-15, and UT-SCC-5 hSCC were injected with pimonidazole hypoxia and Hoechst perfusion markers. Bioluminescence imaging was used to determine spatial distribution of glucose and lactate content in serial tumour sections. Metabolite levels were grouped in 10 concentration ranges. Images were co-registered and at each concentration range the proportion of area stained for pimonidazole and Hoechst was determinedin 1113 tumours per tumour line. Results: The spatia…
Prospective Image Quality and Lesion Assessment in the Setting of MR-Guided Radiation Therapy of Prostate Cancer on an MR-Linac at 1.5 T: A Comparison to a Standard 3 T MRI
The objective of this study is to conduct a qualitative and a quantitative image quality and lesion evaluation in patients undergoing MR-guided radiation therapy (MRgRT) for prostate cancer on a hybrid magnetic resonance imaging and linear accelerator system (MR-Linac or MRL) at 1.5 Tesla. This prospective study was approved by the institutional review board. A total of 13 consecutive patients with biopsy-confirmed prostate cancer and an indication for MRgRT were included. Prior to radiation therapy, each patient underwent an MR-examination on an MRL and on a standard MRI scanner at 3 Tesla (MRI3T). Three readers (two radiologists and a radiation oncologist) conducted an independent qualita…
Conceptual framework for precision cancer medicine in Germany: Consensus statement of the Deutsche Krebshilfe working group ‘Molecular Diagnostics and Therapy’
Precision cancer medicine (PCM) holds great promises to offer more effective therapies to patients based on molecular profiling of their individual tumours. Although the PCM approach seems intuitive, multiple conceptional and structural challenges interfere with the broad implementation of PCM into clinical practice. Accordingly, concerted national and international efforts are needed to guide the further development and broad adoption of PCM in Germany. With support of the 'German Cancer Aid' (Deutsche Krebshilfe [DKH]) a task force 'Molecular Diagnostics and Therapy' was implemented. In two workshops supported by the DKH, delegates from the fourteen comprehensive cancer centresidentified …
Glycolytic metabolism and tumour response to fractionated irradiation.
Abstract Background and purpose To study whether pre-therapeutic lactate or pyruvate predict for tumour response to fractionated irradiation and to identify possible coherencies between intermediates of glycolysis and expression levels of selected proteins. Materials and methods Concentrations of lactate, pyruvate, glucose and ATP were quantified via bioluminescence imaging in tumour xenografts derived from 10 human head and neck squamous cell carcinoma (HNSCC) lines. Tumours were irradiated with 30 fractions within 6weeks. Expression levels of the selected proteins in tumours were measured at the mRNA and protein level. Tumour-infiltrating leucocytes were quantified after staining for CD45…
Pimonidazole labelling and response to fractionated irradiation of five human squamous cell carcinoma (hSCC) lines in nude mice: The need for a multivariate approach in biomarker studies
To investigate the influence on local control after fractionated radiotherapy of hypoxia measured in unirradiated tumours using the hypoxic marker Pimonidazole, using multivariate approaches.Five human squamous cell carcinoma lines (FaDu, UT-SCC-15, UT-SCC-14, XF354, and UT-SCC-5) were transplanted subcutaneously into the right hind-leg of NMRI nude mice. Histological material was collected from 60 unirradiated tumours after injection of Pimonidazole. The relative hypoxic area within the viable tumour area (Pimonidazole hypoxic fraction, pHF) was determined in seven serial 10 microm cross-sections per tumour by fluorescence microscopy and computerized image analysis. Local tumour control wa…