Impact Of Fractionated Irradiation On Tumor Microenvironment In Human Squamous Cells Carcinomas (hSCC) In Nude Mice

Main Category: Radiology / Nuclear Medicine
Also Included In: Cancer / Oncology
Article Date: 22 Sep 2008 - 4:00 PDT

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Evidence shows that pre-treatment tumour hypoxia correlates with poor radiotherapy outcome. Using an hypoxia marker, pimonidazole, it has been shown that biochemical hypoxia in tumours before treatment correlates with local control after radiotherapy. However, biological parameters may change during radiotherapy, including several determinants of tumour microenvironment. The next step is to study whether changes in tumour microenvironment during radiotherapy can provide additional information on treatment outcome and new avenues for treatment modification. As pimonidazole measures all biochemical hypoxic cells and not specifically hypoxic cancer stem cells, which are relevant for local tu¬mour control, pimonidazole hypoxia was compared with radiobiological hypoxic fraction (rHF), which depends on survival of tumour stem cells.

Series of TCD50 assays were performed to determine local control after 30 fractions in 6 weeks and rHFin UT-SCC-14 and FaDu hSCC. In a histological study, hypoxia and perfusion markers were injected at different time points during irradiation with 2-Gy fractions and relative hypoxic area (pHF), relative vascular area (RVA), fraction of perfused vessels (PF), necrotic fraction (NF) were determined.

FaDu tumour was more radioresistant than UT-SCC-14 by a factor of 1.4. This can in part be explained by higher pre-treatment rHFin FaDu by a factor of 1.8. In both tumours a 2.5-fold increase in rHFwas found after irradiation with 15 2-Gy fractions. This increase in rHF was not however reflected by the unchanged (UT-SCC-14) or decreased (FaDu) pHF. Similar pHFduring irradiation for UT-SCC-14, except for a significant increase after 5 fractions, and con¬tinuous decrease in pHFfor FaDu cannot explain the differential response to fractionated irradiation. In two tumour lines radiation caused similar changes in RVA, PFand NF, which also does not explain the difference in radiotherapy outcome.

Based on two tumour lines, modest histological changes during irradiation cannot explain the dramatic increase in rHFand differences in radiotherapy outcome. To determine whether parameters of tumour microenvironment during irradiation better correlate with radiotherapy outcome than pre-treatment measu¬rements, histological evaluation of more tumour lines is required and is currently underway in our laboratory.

Supported by DFG Ba1433/5-1 and in part by the 6th framework EU-project BioCare, proposal No505785.

Ala Yaromina et al. University of Technology Dresden, Medical Faculty C.G. Carus, Dresden, Germany

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