Improving external beam radiotherapy by combination with internal irradiation.

The efficacy of external beam radiotherapy (EBRT) is dose dependent, but the dose that can be applied to solid tumour lesions is limited by the sensitivity of the surrounding tissue. The combination of EBRT with systemically applied radioimmunotherapy (RIT) is a promising approach to increase efficacy of radiotherapy. Toxicities of both treatment modalities of this combination of internal and external radiotherapy (CIERT) are not additive, as different organs at risk are in target. However, advantages of both single treatments are combined, for example, precise high dose delivery to the bulk tumour via standard EBRT, which can be increased by addition of RIT, and potential targeting of micrometastases by RIT. Eventually, theragnostic radionuclide pairs can be used to predict uptake of the radiotherapeutic drug prior to and during therapy and find individual patients who may benefit from this treatment. This review aims to highlight the outcome of pre-clinical studies on CIERT and resultant questions for translation into the clinic. Few clinical data are available until now and reasons as well as challenges for clinical implementation are discussed.

Prognostic value of HIF-1α expression during fractionated irradiation.

BACKGROUND AND PURPOSE: Hypoxia and reoxygenation are important determinants of outcome after radiotherapy. HIF-1α is a key molecule involved in cellular response to hypoxia. HIF-1α expression levels have been shown to change after irradiation. The objective of the present study was to explore the prognostic value of HIF-1α expression during fractionated irradiation. MATERIALS AND METHODS: Six human squamous cell carcinoma models xenografted in nude mice were analysed. Tumours were excised after 3, 5 and 10 fractions. HIF-1α expression was quantified by western blot. For comparative analysis, previously published data on local tumour control data and pimonidazole hypoxic fraction was used. RESULTS: HIF-1α expression in untreated tumours exhibited intertumoural heterogeneity and did not correlate with pimonidazole hypoxic fraction. During fractionated irradiation the majority of tumour models exhibited a decrease in HIF-1α expression, whereas in UT-SCC-5 no change was observed. Neither kinetics nor expression levels during fractionated irradiation correlated with local tumour control. CONCLUSION: Our data do not support the use of HIF-1α determined during treatment as a biomarker to predict outcome after fractionated irradiation.