Tumoural perfusion as measured by dynamic computed tomography in head and neck carcinoma
Introduction
There is evidence that in some human tumours treatment may fail due to the presence of hypoxia. A recent metaanalysis [17] based on previous clinical trials, showed a significant improvement of local control and survival probability when hypoxic cell sensitizers, hyperbaric oxygen or carbogen breathing were applied; these positive results were dominated by tumours localised in the head and neck region. Hypoxic tumours need to be identified and selected for the special measures which exist for dealing with hypoxic cells, but can not be used in all patients.
Direct quantification of tumour oxygenation can be expected to be of important prognostic value. Tumour oxygenation has been measured invasively using oxygen-sensitive needle electrodes in animal tumours and in certain human tumours, like cervix carcinoma [11], sarcomas [6] and recurrent pelvic tumours [9]. A recent study showed that the median of the fraction of pO2 values less than 2.5 mmHg was the strongest independent variable in predicting radiation response of advanced head and neck cancer [16].
There is need for a non-invasive method to measure tumour oxygenation, not only as predictor of outcome, but also to select patients for concomitant radiosensitizing therapy to overcome the hypoxia effect, like breathing carbogen during radiotherapy (RT) or radiosensitizing medication.
Perfusion can be defined as the blood flow through an organ or other tissue of interest per unit of volume. Tumour perfusion and tumoural oxygen concentration are factors which are usually strongly linked, although tumour oxygenation also depends on oxygen consumption by the tumour cells [24].
As tumour perfusion is related to tumour oxygenation, it would be interesting to know if such perfusion measurements can be used as prognostic indicator regarding the outcome of tumours after RT. An estimate of solid organ perfusion is obtainable in humans with modern cross-sectional imaging methods.
Besides an anatomical analysis, a functional analysis of CT images is also possible. After intravenous bolus injection of a iodinated contrast agent, tissue and vessel attenuation (‘density’) changes can be observed during the first pass of this agent by rapid image acquisition at a given anatomical level. Time-density curves can then be constructed for observer-defined regions of interest (ROIs). Within the limits of some assumptions, tissue perfusion can be estimated based on the observed density changes: the time course of the iodine concentration is a measure of the regional perfusion and this concentration is linearly correlated to tissue density.
Several algorithms can be used to measure tissue perfusion with CT. Recently, the feasibility of the ‘gradient-method’ to measure perfusion in head and neck tumours was reported [10].
In this study, the intra- and interobserver variability, as well as the intra- and interpatient variability of CT-determined tumour perfusion in head and neck tumours is evaluated, as well as the preliminary value of this parameter as predictive factor of local failure after treatment by definitive radiotherapy.
Section snippets
Materials and methods
Between March 1995 and June 1997 43 patients with a primary squamous cell carcinoma in the head and neck region had a CT study of the head and neck which included a dynamic CT-acquisition through the region of the tumour during bolus injection of a contrast medium (‘perfusion study’). All these patients were treated with curative intent with RT. One patient was excluded because the RT was interrupted due to treatment intolerance; another patient was excluded because of motion artefacts during
Primary tumour and nodal volume measurements
Mean (primary) tumour volume was 24.8 ml (median, 10.6 ml; range, 0.77–120 ml); mean nodal volume was 10.7 ml (median, 3.1 ml; range, 0–84,2 ml); mean total tumour volume was 35.4 ml (median, 19.6 ml; range, 0.77–165.7 ml).
Local and locoregional control
Up to the end of September 1997, 19 of the 41 investigated patients developed a local recurrence. Ten of the 41 patients developed a neck recurrence; nine of these patients also had a local recurrence. No separate analysis for local and locoregional outcome is reported, as
Discussion
In all but one patient a perfusion rate measurement could be obtained; the excluded patient suffered from a small glottic tumour, not consistently visualised on the successive images obtained during the dynamic CT acquisition. The calculation of the tumour perfusion rate was possible with low intra- and interobserver variability. A substantial intertumoural COV was found, larger than the intratumoural COV. The obtained perfusion rates did not correlate with CT determined primary tumour volume,
Conclusions
Determination of the perfusion rate of head and neck tumours is feasible by dynamic CT, and can be performed during a routine CT study without much supplementary burden for the patient. Calculation of this parameter is relatively easy and cheap. No correlation with tumour volume and a sufficiently large COV were found in this study; this makes CT determined perfusion rate very interesting to consider as a possible prognostic factor. More patients need to be investigated to test the hypothesis
References (24)
- et al.
Intercapillary distance measurement as an indicator of hypoxia in carcinoma of the cervix uteri
Int. J. Radiat. Oncol. Biol. Phys.
(1986) - et al.
Non-invasive tumour perfusion measurement by dynamic CT: preliminary results
Radiother. Oncol.
(1997) - et al.
Phosphorus magnetic resonance spectroscopy in the assessment of head and neck tumors
Int. J. Radiat. Oncol. Biol. Phys.
(1998) - et al.
Tumor perfusion studies using fast magnetic resonance imaging technique in advanced cervical cancer: a new noninvasive predictive assay
Int. J. Radiat. Oncol. Biol. Phys.
(1996) - et al.
Pretreatment oxygenation predicts radiation response in advanced squamous cell carcinoma of the head and neck
Radiother. Oncol.
(1996) - et al.
Modification of hypoxia-induced radioresistance in tumors by the use of oxygen and sensitizers
Semin. Radiat. Oncol.
(1996) - et al.
Variation of vascular density within and between tumours of the uterine cercix and its predictive value for radiotherapy
Int. J. Radiat. Oncol. Biol. Phys.
(1989) - et al.
Prognostic significance of contrast enhancement and tumor demarcation at CT of squamous cell carcinomas of the oral cavity and oropharynx
Acta Radiol.
(1994) - et al.
Volume determinations using computed tomography
Am. J. Roentgenol.
(1982) - et al.
Quantitative assessment of tissue microcirculation by dynamic contrast-enhanced MR imaging
Adv. MRI Contrast
(1994)