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. 1996 Jul;27:S185–S190.

Oxygen distributions partly explain the radiation response of human squamous cell carcinomas.

P Okunieff 1, J de Bie 1, E P Dunphy 1, D J Terris 1, M Höckel 1
PMCID: PMC2149979  PMID: 8763877

Abstract

The oxygen tension of human tumours has often been thought to alter tumour response to radiation therapy. The purpose of this analysis is to determine to what extent the observed results of radiotherapy fit predictions based on in situ human tumour pO2 distributions. The radiation dose-response curve for patients treated with radiation alone for squamous cell cancers of the cervix and oropharynx were calculated based on published data. pO2 histograms were obtained from 30 women with cervical cancer and 11 patients with neck nodes from head and neck cancers. An average of 76 +/- 35 (range 28-174) measurements were made from each patient. Hypoxia was assumed to be a purely dose-modifying factor with a maximum OER of 2.5. Assuming patients are treated with daily radiation doses of 2 Gy, the squamous cell carcinoma alpha/beta ratio is 10 Gy, and that tumours have a mean of 10(8) clonogens, it was possible to estimate tumour control probability. Tumour oxygenation was an extremely important modifier of the slope of the dose-response curve and alone was sufficient to account for the slope of the clinically observed dose-response curve for neck nodes. The response curve for uterine cervical cancers is very shallow, and the oxygen distribution did not completely account for heterogeneity of response of these tumours. The results support the conclusion that oxygen tension distribution is an important modifier of human radiation treatment response.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bataini P., Brugere J., Bernier J., Jaulerry C. H., Picot C., Ghossein N. A. Results of radical radiotherapeutic treatment of carcinoma of the pyriform sinus: experience of the Institut Curie. Int J Radiat Oncol Biol Phys. 1982 Aug;8(8):1277–1286. doi: 10.1016/0360-3016(82)90576-4. [DOI] [PubMed] [Google Scholar]
  2. Denekamp J., Fowler J. F., Dische S. The proportion of hypoxic cells in a human tumor. Int J Radiat Oncol Biol Phys. 1977 Nov-Dec;2(11-12):1227–1228. doi: 10.1016/0360-3016(77)90140-7. [DOI] [PubMed] [Google Scholar]
  3. Finkelstein E., Glatstein E. Seduced by oxygen. Int J Radiat Oncol Biol Phys. 1988 Jan;14(1):205–207. doi: 10.1016/0360-3016(88)90069-7. [DOI] [PubMed] [Google Scholar]
  4. Freyer J. P., Jarrett K., Carpenter S., Raju M. R. Oxygen enhancement ratio as a function of dose and cell cycle phase for radiation-resistant and sensitive CHO cells. Radiat Res. 1991 Sep;127(3):297–307. [PubMed] [Google Scholar]
  5. Gatenby R. A., Coia L. R., Richter M. P., Katz H., Moldofsky P. J., Engstrom P., Brown D. Q., Brookland R., Broder G. J. Oxygen tension in human tumors: in vivo mapping using CT-guided probes. Radiology. 1985 Jul;156(1):211–214. doi: 10.1148/radiology.156.1.4001408. [DOI] [PubMed] [Google Scholar]
  6. Gatenby R. A., Kessler H. B., Rosenblum J. S., Coia L. R., Moldofsky P. J., Hartz W. H., Broder G. J. Oxygen distribution in squamous cell carcinoma metastases and its relationship to outcome of radiation therapy. Int J Radiat Oncol Biol Phys. 1988 May;14(5):831–838. doi: 10.1016/0360-3016(88)90002-8. [DOI] [PubMed] [Google Scholar]
  7. Girinski T., Pejovic-Lenfant M. H., Bourhis J., Campana F., Cosset J. M., Petit C., Malaise E. P., Haie C., Gerbaulet A., Chassagne D. Prognostic value of hemoglobin concentrations and blood transfusions in advanced carcinoma of the cervix treated by radiation therapy: results of a retrospective study of 386 patients. Int J Radiat Oncol Biol Phys. 1989 Jan;16(1):37–42. doi: 10.1016/0360-3016(89)90007-2. [DOI] [PubMed] [Google Scholar]
  8. Hendry J. H., Thames H. D. Fractionation sensitivity and the oxygen effect. Br J Radiol. 1990 Jan;63(745):79–80. doi: 10.1259/0007-1285-63-745-79. [DOI] [PubMed] [Google Scholar]
  9. Henk J. M., Smith C. W. Radiotherapy and hyperbaric oxygen in head and neck cancer. Interim report of second clinical trial. Lancet. 1977 Jul 16;2(8029):104–105. doi: 10.1016/s0140-6736(77)90117-9. [DOI] [PubMed] [Google Scholar]
  10. Höckel M., Knoop C., Schlenger K., Vorndran B., Baussmann E., Mitze M., Knapstein P. G., Vaupel P. Intratumoral pO2 predicts survival in advanced cancer of the uterine cervix. Radiother Oncol. 1993 Jan;26(1):45–50. doi: 10.1016/0167-8140(93)90025-4. [DOI] [PubMed] [Google Scholar]
  11. Höckel M., Schlenger K., Knoop C., Vaupel P. Oxygenation of carcinomas of the uterine cervix: evaluation by computerized O2 tension measurements. Cancer Res. 1991 Nov 15;51(22):6098–6102. [PubMed] [Google Scholar]
  12. Höckel M., Vorndran B., Schlenger K., Baussmann E., Knapstein P. G. Tumor oxygenation: a new predictive parameter in locally advanced cancer of the uterine cervix. Gynecol Oncol. 1993 Nov;51(2):141–149. doi: 10.1006/gyno.1993.1262. [DOI] [PubMed] [Google Scholar]
  13. Lee D. J., Cosmatos D., Marcial V. A., Fu K. K., Rotman M., Cooper J. S., Ortiz H. G., Beitler J. J., Abrams R. A., Curran W. J. Results of an RTOG phase III trial (RTOG 85-27) comparing radiotherapy plus etanidazole with radiotherapy alone for locally advanced head and neck carcinomas. Int J Radiat Oncol Biol Phys. 1995 Jun 15;32(3):567–576. doi: 10.1016/0360-3016(95)00150-W. [DOI] [PubMed] [Google Scholar]
  14. Moulder J. E., Rockwell S. Hypoxic fractions of solid tumors: experimental techniques, methods of analysis, and a survey of existing data. Int J Radiat Oncol Biol Phys. 1984 May;10(5):695–712. doi: 10.1016/0360-3016(84)90301-8. [DOI] [PubMed] [Google Scholar]
  15. Müller H., Brock M., Ernst H. Long-term survival and recurrence-free interval in combined surgical, radio- and chemotherapy of malignant brain gliomas. Clin Neurol Neurosurg. 1985;87(3):167–171. doi: 10.1016/0303-8467(85)90002-2. [DOI] [PubMed] [Google Scholar]
  16. Okunieff P. G., Koutcher J. A., Gerweck L., McFarland E., Hitzig B., Urano M., Brady T., Neuringer L., Suit H. D. Tumor size dependent changes in a murine fibrosarcoma: use of in vivo 31P NMR for non-invasive evaluation of tumor metabolic status. Int J Radiat Oncol Biol Phys. 1986 May;12(5):793–799. doi: 10.1016/0360-3016(86)90038-6. [DOI] [PubMed] [Google Scholar]
  17. Okunieff P., Hoeckel M., Dunphy E. P., Schlenger K., Knoop C., Vaupel P. Oxygen tension distributions are sufficient to explain the local response of human breast tumors treated with radiation alone. Int J Radiat Oncol Biol Phys. 1993 Jul 15;26(4):631–636. doi: 10.1016/0360-3016(93)90280-9. [DOI] [PubMed] [Google Scholar]
  18. Okunieff P., Urano M., Kallinowski F., Vaupel P., Neuringer L. J. Tumors growing in irradiated tissue: oxygenation, metabolic state, and pH. Int J Radiat Oncol Biol Phys. 1991 Aug;21(3):667–673. doi: 10.1016/0360-3016(91)90685-w. [DOI] [PubMed] [Google Scholar]
  19. Overgaard J. Sensitization of hypoxic tumour cells--clinical experience. Int J Radiat Biol. 1989 Nov;56(5):801–811. doi: 10.1080/09553008914552081. [DOI] [PubMed] [Google Scholar]
  20. Perez C. A., Kao M. S. Radiation therapy alone or combined with surgery in the treatment of barrel-shaped carcinoma of the uterine cervix (stages IB, IIA, IIB). Int J Radiat Oncol Biol Phys. 1985 Nov;11(11):1903–1909. doi: 10.1016/0360-3016(85)90270-6. [DOI] [PubMed] [Google Scholar]
  21. Peters L. J., Brock W. A., Johnson T., Meyn R. E., Tofilon P. J., Milas L. Potential methods for predicting tumor radiocurability. Int J Radiat Oncol Biol Phys. 1986 Apr;12(4):459–467. doi: 10.1016/0360-3016(86)90053-2. [DOI] [PubMed] [Google Scholar]
  22. Peters L. J., Brock W., Johnson T. Predicting radiocurability. Cancer. 1985 May 1;55(9 Suppl):2118–2122. doi: 10.1002/1097-0142(19850501)55:9+<2118::aid-cncr2820551414>3.0.co;2-d. [DOI] [PubMed] [Google Scholar]
  23. Suit H. D., Sedlacek R., Silver G., Hsieh C. C., Epp E. R., Ngo F. Q., Roberts W. K., Verhey L. Therapeutic gain factors for fractionated radiation treatment of spontaneous murine tumors using fast neutrons, photons plus O2(1) or 3 ATA, or photons plus misonidazole. Radiat Res. 1988 Dec;116(3):482–502. [PubMed] [Google Scholar]
  24. Suit H., Skates S., Taghian A., Okunieff P., Efird J. T. Clinical implications of heterogeneity of tumor response to radiation therapy. Radiother Oncol. 1992 Dec;25(4):251–260. doi: 10.1016/0167-8140(92)90244-o. [DOI] [PubMed] [Google Scholar]
  25. Tucker S. L., Thames H. D., Taylor J. M. How well is the probability of tumor cure after fractionated irradiation described by Poisson statistics? Radiat Res. 1990 Dec;124(3):273–282. [PubMed] [Google Scholar]
  26. Vaupel P., Kallinowski F., Okunieff P. Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: a review. Cancer Res. 1989 Dec 1;49(23):6449–6465. [PubMed] [Google Scholar]
  27. Vaupel P., Okunieff P., Neuringer L. J. Blood flow, tissue oxygenation, pH distribution, and energy metabolism of murine mammary adenocarcinomas during growth. Adv Exp Med Biol. 1989;248:835–845. doi: 10.1007/978-1-4684-5643-1_95. [DOI] [PubMed] [Google Scholar]
  28. Vaupel P., Schlenger K., Hoeckel M. Blood flow and tissue oxygenation of human tumors: an update. Adv Exp Med Biol. 1992;317:139–151. doi: 10.1007/978-1-4615-3428-0_14. [DOI] [PubMed] [Google Scholar]
  29. Watson E. R., Halnan K. E., Dische S., Saunders M. I., Cade I. S., McEwen J. B., Wiernik G., Perrins D. J., Sutherland I. Hyperbaric oxygen and radiotherapy: a Medical Research Council trial in carcinoma of the cervix. Br J Radiol. 1978 Nov;51(611):879–887. doi: 10.1259/0007-1285-51-611-879. [DOI] [PubMed] [Google Scholar]
  30. West C. M., Davidson S. E., Hunter R. D. Evaluation of surviving fraction at 2 Gy as a potential prognostic factor for the radiotherapy of carcinoma of the cervix. Int J Radiat Biol. 1989 Nov;56(5):761–765. doi: 10.1080/09553008914552011. [DOI] [PubMed] [Google Scholar]

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