Radiobiological Hypoxia, Oxygen Tension, Interstitial Fluid Pressure and Relative Viable Tumour Area in Two Human Squamous Cell Carcinomas in Nude Mice During Fractionated Radiotherapy

Abstract

Very little is known about the correlation between the radiobiological hypoxic fraction (rHF) and other measures of tumour oxygenation during fractionated irradiation. In the present study the rHF is determined in untreated human FaDu and GL squamous cell carcinoma in nude mice and in tumours irradiated with 10 fractions in 2 weeks and 20 fractions in 4 weeks, using tumour control as the experimental endpoint. The results were compared with measurements of the pO2, the interstitial fluid pressure (IFP) and the relative viable tumour area. In FaDu tumours the radiobiological hypoxic fractions (rHFs) before and during irradiation were not statistically different from 100%. Depending on the assumptions made for D0, the rHFs of GL tumours were between 0.2 and 4% or 30 and 53%. The median pO2 values were 2.8 mmHg for untreated FaDu tumours and 0.2 mmHg for GL tumours (p < 0.001). The median IFP values were 2.6 mmHg in FaDu and 5.3 mmHg in GL tumours (p = 0.01). No important changes in the pO2 and IFP values were observed during fractionated irradiation. The relative viable tumour area during irradiation decreased by 83% in FaDu tumours (p = 0.002) and by 54% in GL tumours (p = 0.003). It is concluded that differences in rHF exist between FaDu and GL tumours before and during fractionated irradiation and that these differences are not reflected by pO2 and IFP values and the relative viable tumour area.

Exploratory Study of the Prognostic Value of Microenvironmental Parameters During Fractionated Irradiation in Human Squamous Cell Carcinoma Xenografts

“…For example, in SAS pHV transiently increased after five fractions and returned to baseline level later during the course of treatment. This intertumoral heterogeneity in the kinetics of oxygenation during fractionated irradiation is in line with the findings of experimental and clinical studies (11,(18)(19)(20)(21)(23)(24)(25). In our study, improved tumor oxygenation shown by the decrease in pimonidazole hypoxia indicates that effective reoxygenation occurred during treatment.…”

“…These results indicate a limited prognostic value of these parameters when determined before fractionated irradiation. Experimental and clinical studies demonstrated that after single-dose and fractionated irradiation parameters of the tumor microenvironment, such as hypoxic fraction, vasculature, and perfusion, might change and have an impact on radiation response (11,(17)(18)(19)(20)(21)(22)(23)(24)(25)(26). To explore the prognostic value of the microenvironmental parameters during fractionated irradiation, we selected six hSCC from the previously studied panel with different radiation sensitivity and measured hypoxia, perfusion and vasculature before and during fractionated irradiation.…”

Mitomycin C in combination with radiotherapy as a potent inhibitor of tumour cell repopulation in a human squamous cell carcinoma

“…In contrast to Baumann et al (1994), radiotherapy (top up) in the present study was administered under acutely hypoxic conditions. Under these conditions, However, according to the data of Baumann et al (2001), the hypoxic fraction of surviving clonogenic tumour cells at the end of the fractionated radiotherapy is close to 100% in FaDu dd tumours on nude mice. These data gave indirect evidence that top up irradiations under ambient conditions might have given identical results and that our results are entirely consistent with results of Baumann et al (1994Baumann et al ( , 2001.…”

“…Under these conditions, However, according to the data of Baumann et al (2001), the hypoxic fraction of surviving clonogenic tumour cells at the end of the fractionated radiotherapy is close to 100% in FaDu dd tumours on nude mice. These data gave indirect evidence that top up irradiations under ambient conditions might have given identical results and that our results are entirely consistent with results of Baumann et al (1994Baumann et al ( , 2001. The dose needed to counteract tumour cell repopulation can be calculated from the CHART (Dische et al, 1997) and V-CHART (Dobrowsky and Naude, 2000) clinical trials.…”

MR perfusion measurements on pharyngeal tumors: Comparison of quantification strategies

“…In a study of the physiology of pharyngeal tumors (approved by the ethics commission of the University Hospital “Carl Gustav Carus” at the Technical University of Dresden), ( 5 ) the invasively measured extracellular oxygen partial pressure in the tumor tissue was determined. Its polarographical measurement is the gold standard for the description of tumor oxygenation (many other methods, such as oxygen tension, interstitial fluid pressure, and vital tumor fraction, do not correlate to the measured data by means of ${\text{pO}}_2$ probes ( 6 ) ). Glucose metabolism activity was described by means of positron emission tomography (PET).…”