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Potential for EPR Oximetry to Guide Treatment Planning for Tumors

  • Julia A. O’Hara
  • Fuminori Goda
  • Jeffrey F. Dunn
  • Harold M. Swartz
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 411)

Abstract

A major contributing factor in the failure of solid tumors to be locally controlled by radiation therapy (RT) is the relative radiation resistance of hypoxic cells of tumors compared to well-oxygenated cells. Recently clinical studies have established the presence of hypoxic regions in human tumors (1,2). Further studies confirmed that relatively high tissue pO2 in human tumors correlated with positive outcomes of radiation therapy and that poor outcomes were associated with tumors with low pO2 (3–6). As a result of available studies, the conclusion has been drawn that the effective level of oxygenation in individuals could not be predicted based on tumor type, histology, staging, or even size, but had to be measured (7). With the development of methods to measure the pO2 in tumors (8), it now seems feasible to determine if this parameter, which can be of crucial importance in radiation therapy, can be used to improve treatment by permitting individualized optimization of therapy on the basis of the pO2 in the tumor.

Keywords

Electron Paramagnetic Resonance Hypoxic Fraction Dartmouth Medical School Tumor Volume Change Electron Paramagnetic Resonance Oximetry 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    R. A. Gatenby, L. R. Coia, M. P. Richter, H. Katz, P. J. Moldofsky, P. Engstrom, D. Q. Brown, R. Brook-land and G. J. Broder, Oxygen tension in human tumors: In vivo mapping using CT-guided probes. Radiology. 156, 211–214 (1985).PubMedGoogle Scholar
  2. 2.
    M. Hockel, K. Schienger, C. Knoop and P. Vaupel, Oxygenation of carcinomas of the uterine cervix: evaluation by computerized O2 tension measurements. Cancer Research. 51, 6098–6102 (1991).PubMedGoogle Scholar
  3. 3.
    P. Okunieff, M. Hoeckel, E. P. Dunphy, K. Schlenger, C. Knoop and P. Vaupel, Oxygen tension distributions are sufficient to explain the local response of human breast tumors treated with radiation alone. Int J Radiat Oncol Biol Phys. 26,(4), 631–636 (1993).PubMedCrossRefGoogle Scholar
  4. 4.
    M. Hockel, C. Knoop, K. Schlenger, B. Vorndran, E. Baussmann, M. Mitze, P. G. Knapstein and P. Vaupel, Intratumoral pO2 predicts survival in advanced cancer of the uterine cervix. Radiother Oncol. 26,(1), 45–50 (1993).PubMedCrossRefGoogle Scholar
  5. 5.
    E. Lartigau, A. M. Le Ridant, P. Lambin, P. Weeger, L. Martin, R. Sigal, A. Lusinchi, B. Luboinski, F. Eschwege and M. Guichard, Oxygenation of head and neck tumors. Cancer. 71,(7), 2319–2325 (1993).PubMedCrossRefGoogle Scholar
  6. 6.
    R. A. Gatenby, H. B. Kessler, J. S. Rosenblum, L. R. Coia and P. J. Broder, Oxygen distribution in squamous cell carcinoma metastases and its relationship to outcome of radiation therapy. Int J Radiat Oncol Biol Phys. 14, 831–838 (1987).CrossRefGoogle Scholar
  7. 7.
    P. W. Vaupel, Oxygenation of solid tumors. In Drug Resistance in Oncology (B. A. Teicher, Ed.), pp. 53–86. Marcel Dekker, New York, 1993.Google Scholar
  8. 8.
    H. B. Stone, J. M. Brown, T. L. Phillips and R. M. Sutherland, Oxygen in human tumors: correlations between methods of measurement and response to therapy. Summary of a workshop held November 19–20, 1992, at the National Cancer Institute, Bethesda, Maryland. Radiat Res. 136,(3), 422–434 (1993).PubMedCrossRefGoogle Scholar
  9. 9.
    J. A. O’Hara, F. Goda, K. J. Liu, G. A. Bacic, P. J. Hoopes and H. M. Swartz, Oxygenation in a murine tumor following radiation: an in vivo electron paramagnetic resonance oximetry study. Radiat Res. 144,(2), 222–229 (1995).PubMedCrossRefGoogle Scholar
  10. 10.
    F. Goda, J. A. O’Hara, E. S. Rhodes, K. J. Liu, J. F. Dunn, G. Bacic and H. M. Swartz, Changes of oxygen tension in experimental tumors after a single dose of X-ray irradiation. Cancer Res. 55, (1 Jun), 2249–2252 (1995).Google Scholar
  11. 11.
    E. J. Hall, Radiobiology for the Radiologist. In Ed.), pp. 143. JB Lippincott, Philadelphia, 1988.Google Scholar
  12. 12.
    L. M. Van Putten and R. F. Kallman, Oxygenation status of a transplantable tumor during fractionated radiation therapy. JNCI. 140,(3), 441–451 (1968).Google Scholar
  13. 13.
    J. E. Moulder and S. Rockwell, Hypoxic fractions of solid tumors: experimental techniques, methods of analysis and a survey of existing data. Int J Radiat Oncol Biol Phys. 10, 695–712 (1984).PubMedCrossRefGoogle Scholar
  14. 14.
    M. R. Horsman, A. A. Khalil, D. W. Siemann, C. Grau, S. A. Hill, E. M. Lynch, D. J. Chaplin and J. Over-gaard, Relationship between radiobiological hypoxia in tumors and electrode measurements of tumor oxygenation. Int J Radiat Oncol Biol Phys. 29,(3), 439–442 (1994).PubMedCrossRefGoogle Scholar
  15. 15.
    K. Sasai and J. M. Brown, Discrepancies between measured changes of radiobiological hypoxic fraction and oxygen tension monitoring using two assay systems. Int J Radiat Oncol Biol Phys. 30,(2), 355–361 (1994).PubMedCrossRefGoogle Scholar
  16. 16.
    R. K. Jain, Physiological resistance to the treatment of solid tumors. In Drug Resistance in Oncology (B. A. Teicher, Ed.), pp. 87–105. Marcel Dekker, New York, 1993.Google Scholar
  17. 17.
    J. E. Moulder and S. Rockwell, Tumor hypoxia: its impact on cancer therapy. Cancer and metastasis reviews. 5, 313–342 (1987).PubMedCrossRefGoogle Scholar
  18. 18.
    I.J. Stratford, Bioreductive drugs in cancer therapy. Br J Radiol. Suppl, (24), 128–13 (1992).Google Scholar
  19. 19.
    J. M. Brown and M. J. Lemmon, Tumor hypoxia can be exploited to preferentially sensitize tumors to fractionated irradiation [see comments]. Int J Radiat Oncol Biol Phys. 20,(3), 457–461 (1991).PubMedCrossRefGoogle Scholar
  20. 20.
    R. E. Durand and N. E. LePard, Modulation of tumor hypoxia by conventional chemotherapeutic agents. Int J Radiat Oncol Biol Phys. 29,(3), 481–486 (1994).PubMedCrossRefGoogle Scholar
  21. 21.
    M. J. Dorie and R. F. Kallman, Reoxygenation in the RIF-1 tumor after chemotherapy. Int J Radiat Oncol Biol Phys. 24,(2), 295–299 (1992).PubMedCrossRefGoogle Scholar
  22. 22.
    E. Jahde, S. Roszinski, T. Volk, K. H. Glusenkamp, G. Wiedemann and M. F. Rajewsky, Metabolic response of AH13r rat tumours to cyclophosphamide as monitored by pO2 and pH semi-microelectrodes. Eur J Cancer. 1, 116–122 (1992).Google Scholar
  23. 23.
    L. Milas, N. Hunter, K. A. Mason, C. Milross and L. J. Peters, Tumor reoxygenation as a mechanism of taxol-induced enhancement of tumor radioresponse. Acta Oncol. 34,(3), 409–412 (1995).PubMedCrossRefGoogle Scholar
  24. 24.
    B. A. Teicher, N. P. Dupuis, T. Kusumoto, M. Liu, F. Liu, K. Menon, G. N. Schwartz and I. E Frei, Decreased tumor oxygenation after cyclophosphamide, reoxygenation and therapeutic enhancement with a perflubron emulsion/carbogen breathing. Int J Oncol. 3, 197–203 (1993).PubMedGoogle Scholar
  25. 25.
    M. Busse and P. W. Vaupel, The role of tumor volume in ‘reoxygenation’ upon cyclophosphamide treatment. Acta Oncologica. 34,(3), 405–408 (1995).PubMedCrossRefGoogle Scholar
  26. 26.
    T. L. Phillips, Terminology for chemoradiation effects. In Chemoradiation: An Integrated Approach to Cancer Treatment (M. J. John, Ed.), pp. 11–17. Lea & Febiger, Philadelphia, 1993.Google Scholar
  27. 27.
    W. B. Looney and H. A. Hopkins, Rationale for different chemotherapeutic and radiation therapy strategies in cancer management. Cancer. 67,(6), 1471–1483 (1991).PubMedCrossRefGoogle Scholar
  28. 28.
    G. G. Steel and M. J. Peckham, Exploitable mechanisms in combined radiotherapy-chemotherapy: The concept of additivity. Int J Radiat Oncol Biol Phys. 5, 85 (1979).PubMedCrossRefGoogle Scholar
  29. 29.
    G. G. Steel, The combination of radiotherapy and chemotherapy. In The Biological Basis of Radiotherapy (G. G. Steel, G. E. Adams, and M. J. Peckham, Ed.), pp. 239–248. Elsevier, Amsterdam, 1983.Google Scholar
  30. 30.
    H. M. Swartz, G. Bacic, B. Friedman, F. Goda, O. Grinberg, P. J. Hoopes, J. Jiang, K. J. Liu, T. Nakashima, J. A. O’Hara and T. Walczak, Measurements of pO2 in vivo, including human subjects, by electron paramagnetic resonance. In Oxygen Transport to Tissue (e. a. M.C. Hogan, Ed.), pp. 119–128. Plenum Press, New York, 1994.Google Scholar
  31. 31.
    H. M. Swartz, K. J. Liu, F. Goda and T. Walczak, India ink: A potential clinically applicable EPR oximetry probe. Magn Reson Med. 31,(2), 229–232 (1994).PubMedCrossRefGoogle Scholar
  32. 32.
    W. B. Looney, H. A. Hopkins and M. Tubiana, Experimental and clinical studies alternating chemotherapy and radiotherapy. Cancer Metastasis Rev. 8,(1), 53–79 (1989).PubMedCrossRefGoogle Scholar
  33. 33.
    B. A. Teicher, S. A. Holden, S. M. Jones, J. P. Eder and T. S. Herman, Influence of scheduling on two-drug combinations of alkylating agents in vivo. Cancer Chemother Pharmacol. 25,(3), 161–166 (1989).PubMedCrossRefGoogle Scholar
  34. 34.
    R. F. Kallman, D. Rapacchietta and M. S. Zaghloul, Schedule-dependent therapeutic gain from the combination of fractionated irradiation plus c-DDP and 5-FU or plus c-DDP and cyclophosphamide in C3H/ Km mouse model systems. Int J Radiat Oncol Biol Phys. 20,(2), 227–232 (1991).PubMedCrossRefGoogle Scholar
  35. 35.
    P. G. Braunschweiger, Effect of cyclophosphamide on the pathophysiology of RIF-1 solid tumors. Cancer Res. 48, 4206–4210 (1988).PubMedGoogle Scholar
  36. 36.
    A. C. Begg, K. K. Fu, D. C. Shrieve and T. L. Phillips, Combination therapy of a solid murine tumor with cyclophosphamide and radiation: The effects of time, dose and assay method. Int J Radiat Oncol Biol Phys. 5, 1433–1439 (1979).PubMedCrossRefGoogle Scholar
  37. 37.
    P. Twentyman, Timing of Assays: an important consideration in the determination of clonogenic cell survival both in vitro and in vivo. Int J Radiat Oncol Biol Phys. 5, 1213–1220 (1979).PubMedCrossRefGoogle Scholar
  38. 38.
    K. H. Clifton, R. C. Briggs and H. B. Stone, Quantitative radiosensitivity studies of solid carcinomas in vivo: methodology and effect of anoxia. J Natl Canc Inst. 36, 965–974 (1966).Google Scholar
  39. 39.
    E. Jones, B. Lyons, E. Douple, A. Filimonov and B. Dain, Response of a brachytherapy model using 125I in a murine tumor system. Rad Res. 118, 112–130 (1989).CrossRefGoogle Scholar
  40. 40.
    E. B. Douple, J. A. O’Hara and E. L. Jones, Paraplatin enhancement of radiation therapy in a murine tumor (MTG-B). In Anticancer Drug Research (K. Lapis S. Eckhardt, Ed.), pp. 71–80. Akademiai Kiado, Budapest, 1987.Google Scholar
  41. 41.
    F. Goda, K. J. Liu, T. Walczak, J. A. O’Hara and H. M. Swartz, In vivo oximetry using EPR and India ink. Magn Reson Med. 33,(2), 237–245 (1995).PubMedCrossRefGoogle Scholar
  42. 42.
    D. Hand and C. C. Taylor, Multivariate Analysis of Variance and Repeated Measures, ed. Chapman and Hall, New York, 1987.CrossRefGoogle Scholar
  43. 43.
    S. L. Zeger and K. Y. Liang, Longitudinal data analysis for discrete and continuous outcomes. Biometrics. 42, 121–130 (1986).PubMedCrossRefGoogle Scholar
  44. 44.
    M. J. Dorie and R. F. Kallman, Reoxygenation of the RIF-1 tumor after fractionated radiotherapy. Int J Radiat Oncol Biol Phys. 12, 1853–1859 (1986).PubMedCrossRefGoogle Scholar
  45. 45.
    J. Neter, W. Wasserman and M. H. Kutner, Applied Linear Statistical Models, 2nd ed. RD Irwin Inc, Home-wood, IL, 1985.Google Scholar
  46. 46.
    J. A. O’Hara, F. Goda and H. M. Swartz, The pO2 changes in RIF-1 tumors after combined therapy with cyclophosphamide and radiation. Br J Canc. Submitted, (1995).Google Scholar
  47. 47.
    M. R. Horsman, C. Grau and J. Overgaard, Reoxygenation in a C3H mouse mammary carcinoma. The importance of chronic rather than acute hypoxia. Acta Oncol. 34,(3), 325–328 (1995).PubMedCrossRefGoogle Scholar
  48. 48.
    W. B. Looney and H. A. Hopkins, Experimental and clinical rationale for alternating chemotherapy and radiotherapy in human cancer management. In Chemoradiation: An Integrated Approach to Cancer Management (M. J. John, Ed.), pp. 27–51. Lea & Febiger, Philadelphia, 1993.Google Scholar
  49. 49.
    P. R. Twentyman, R. F. Kallman and J. M. Brown, The effect of time between x-irradiation and chemotherapy on the growth of three solid mouse tumors. II. Cyclophosphamide. Int J Radiat Oncol Biol Phys. 5, 1425–1427 (1979).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • Julia A. O’Hara
    • 1
  • Fuminori Goda
    • 2
  • Jeffrey F. Dunn
    • 2
  • Harold M. Swartz
    • 2
  1. 1.Department of Medicine (Radiation Oncology)Dartmouth Medical School, Norris Cotton Cancer CenterHanoverUSA
  2. 2.Department of Diagnostic RadiologyDartmouth Medical School, Norris Cotton Cancer CenterHanoverUSA

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