1628

1. J. Radiation

Oncology

0 Biology 0 Physics

3. Vegesna. V.; Withers. H. R.; Thames, H. D. Multifraction Radiation Response of mouse lung. Int. J. Radiat. Biol. 55:2100-2104; 1985. 4. Withers, H. R.; Horiot, J. C. Hiperfractionation. Innovations in Radiation Oncology. Berlin, Heidelberg, New York: Springer-Verlag: 1988:223-230. 5. Withers, H. R.: Mason. K. A.; Thames. H. D. Late radiation response of kidney assayed by tubule cell survival. Dr. J. Radiol. 59:587-595: 1986.

02 LEVELS

TISSUES

IN NORMAL

To thu Editor: We read with interest the article ‘Induction of severe tumor hypoxia by modifiers of the oxygen affinity of hemoglobin’ by G. E. Adams et al., in which they describe the use of BW589C to induce tumor hypoxia for use in conjunction with cytotoxic bioreductive drugs. Their rationale for its use rests to some extent on its effect on the shape of the oxygen/hemoglobin association curve. The left shift effect is clearly asymmetric, and the authors argue that this will produce a differential effect between tumors and normal tissue. The displacement of the association curve is much less at higher oxygen levels, that is to say between 80 and 100 mmHg. than at the lower oxygen levels found in tumors. This is certainly the case, but we question the assumption that normal tissues are at such high levels of oxygenation. Data from oxygen electrode measurements suggest that OZ levels in normal tissues may be very heterogeneous and lower than is generally expected, possibly falling within the range of radiobiological hypoxia. Hasegawa et al. (6) records a median 02 tension in muscle of 14.9 mmHg. which corresponds with data from Kallinowski and Vaupel (7). who found a range of O2 tensions of between 0 and 100 mmHg with a mean of 29 mmHg, again in muscle. Similarly. the data reported by Cater and Silver (4) found O2 levels of 14.3 mmHg in muscle and 15.5 mmHg in bone marrow. Bicher et al. (2) recording from cat brain, measured oxygen tensions ranging from 2-95 mmHg, and Bohlen (3) recorded mean PO? levels of 26.4 f 1.6 mmHg in the muscle and submucosa of rat small intestine and 14.8 + 1.2 mmHg in the villus apex. Many other authors have reported similar levels in normal tissue (5). and reference to the oxygen-hemoglobin association curves illustrated in the paper would suggest that at these levels of oxygen tension, the shift in the curve is actually greater than that which occurs at the lower oxygen tensions found in tumours (Fig. I ). If this is indeed the case. then is it possible that the therapeutic index described would be lost?

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Fig. 1. Displacement of oxygen-haemoglobin after 250 mg/kg BW589C relative to control.

association

curve 8 hours

A. E. BREWSTER J. L. MOORE Department of Radiobiology South Wales Regional Centre for Radiotherapy and Oncology Cardiff. CF4 7XL. UK

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December

1990, Volume

19, Number

6

I. Adams, G. E.; Stratford. I. J.: Nethersell. A. B. W.; White. R. D. Induction of severe hypoxia by modifiers of the oxygen affinity of hemoglobin. Int. J. Radiat. Oncol. Biol. Phvs. 16: I I79- I 182; 1989. 2. Biche; H. 1.; Bruley, D. F.: Reneau, D. D.: Knisely. M. H. Effect of microcirculation changes on brain tissue oxygenation. J. Physiol. 217:689-707; 1971. 3. Bohlen. H. G. Intestinal tissue PO2 and microvascular responses during glucose exposure. Am. J. Physiol. 238:Hl64-171; 1980. 4. Cater. D.: Silver. I. A. Quantitative measurements ofoxygen tension in normal tissues and in the tumours of patients before and after radiotherapy. Alta. Radiol. 53:233-256; 1960. Fatt, I. (I 976). Oxygen tension measurements in malignant tissue in Polarographic oxygen sensors. CRC Press. Cleveland. Ohio. Hasegawa, T.: Rhee. J. G.; Levitt. S. H.; Song. C. W. Increase in tumour p02 by perfluorochemicals and carbogen. Int. J. Radiat. Oncol. Biol. Phys. 13:569-574; 1987. Kallinowski. F.: Vaupel. P. Concurrent measurements of 0, partial pressures and pH values in human mammary carcinoma xenotransplants. Adv. Exp. Med. Biol. 200:609-621: 1986. Stokes, B. T.; Garwood, M.: Walters. P. Oxygen fields in specific spinal loci of the canine spinal cord. Am. J. Physiol. 240:H76 l-766; 1981.

ENDOBRONCHIAL

IRRADIATION

To fk Editor: According to Mehta (‘I al. (3). afterloading endobronchial irradiation represents a highly effective palliative modality for recurrent non-small cell lung cancer and other malignant airway obstructions. Macha el ul. (2) and Alberti et al. (I) have demonstrated that endobronchial irradiation with a remote controlled high dose rate (HDR) afterloading device* has several advantages compared to the afterloading technique using Ir-192 implants in polyethylene catheters: 1. Treatment can be performed on an out-patient basis which makes it more convenient for the patient and reduces hospitalization costs significantly. Due to the high activity source the total time for delivery of irradiation varies from 3 to 5 minutes depending on source strength and extent of tumor. This is significantly less than the median implant duration of 50.5 hrs (11 to I 15 hrs) as in the study by Mehta et u/. (3). 2. Because HDR afterloading devices are now utilized in many institutions for the treatment of uterine carcinoma. there is no additional capital expense and amortization will be more broadly based. 3. The radiation exposure of the staff is reduced markedly. 4a. The short treatment time permits fractionated irradiation e.g. once or twice weekly. 4b. If both main bronchi and the trachea are involved, sequential irradiation in one session can be performed. Regardless of the modality used, it is important to define the indication for an endobronchial irradiation accurately in order to avoid fatal complications: A complete stenosis caused by endobronchial tumor growth should be lasered sparingly. Considering that the flexible afterloading catheter which serves as a guide for an iridium-192 source (diameter 1.1 mm). has an outer diameter ofonly 2 mm. a relatively small bronchus opening is sufficient. In the case of advanced recurrent non-small tumors a DSA should be performed to exclude patients with involvement of the pulmonary artery who run the risk of fatal bleeding. Patients with nonperfusion of the ipsilateral lung should not be treated with endobronchial irradiation since they will not benefit from improvement of ventilation. Patients with poststenotic pneumonia are an exception: they will not have to be hospitalized as often. once the stenosis is opened. In the case of compression caused by extrabronchial tumor growth. the palliative effect of endobronchial irradiation is of debatable value. It may. nevertheless, be attempted in recurrent disease. if external beam therapy preceeded. In general. external beam radiotherapy should be used as primary treatment before employing endobronchial irradiation. Exceptions to this procedure should be made for patients suffering from poor ventilation which thus contraindicates external beam therapy if a larger lung volume must be included. According to our present experiences, quality of life may be improved but not survival. When considering the limitations described above, we

O2 levels in normal tissues.

1628 1. J. Radiation Oncology 0 Biology 0 Physics 3. Vegesna. V.; Withers. H. R.; Thames, H. D. Multifraction Radiation Response of mouse lung. In...
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