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Radiation therapy under hyperbaric oxygen
Int
J
Radiation
Oncology Biol. Phys , 1977, Vol. 2, pp.
819-820.
Pergamon
Press.
Printed
in the U.S.A
0 Editorial
RADIATION
THERAPY
UNDER HYPERBARIC
HENRY P. PLENK, Director.
Radiation
therapy,
Radiation
Hyperbaric
Center.
OXYGEN
M.D.
LDS Hospital. 335 8th Ave.. UT X4143. U.S.A.
Salt Lake City.
oxygen.
the treatment of carcinoma of the cervix, revealed no difference in results. On the other hand, Henk? using a short-fractionation schedule, reported the most impressive data with hyperbaric oxygen to date in the treatment of head and neck cancer. A large randomized trial comparing ten fractions of approximately 400 rad in 3 weeks, with a comparable technique in air, or 30 treatments in air, demonstrated a significant difference in favor of oxygen in the local tumor control rate. While the survivals in the oxygen group were better than those in air, the difference was not significant since a larger number of patients in the air group required salvage surgery, which was successful in many patients; however, when comparing the results in earlier stages of tumors, significant improvement was observed in the oxygen group. The importance of using fewer large fractions in order to take advantage of the maximal oxygen enhancement ratio has been pointed out by Withers and Scott,” RCv&z and Littbrand’ and Nias,’ but has been overlooked in the design of many randomized trials. Only with the use of optimal short-fractionation schedules can we expect to get the greatest benefits from the use of hyperbaric oxygen in radiation therapy. It is hoped that this paper, as well as the experience of Henk,4 Chang et al.,’ Plenk,h Glassburn, Brady and Plenk.7 as well as papers to be published in a forthcoming British Empire Cancer Campaign report, will encourage further randomized studies comparing optimal treatment techniques with hyperbaric oxygen using fewer, larger fractions with optimal treatment techniques in air. While neutrons, radiation sensitizers or hyperthermia may, in the long run, give results equal to, or better than those achieved with hyperbaric oxygen, the full use of hyperbaric oxygen certainly should be pursued, especially by those centers that already have tanks at their disposal, until other available methods can be proven to be superior.
Only a handful of centers in the United States have explored the usefulness of hyperbaric oxygen in the radiation therapy of cancer; very few randomized studies have been conducted in this country. Most studies have come from Great Britain, some from Australia, Canada, South Africa and Japan. The paper by Sealy et al..’ in this issue describes the results in comparable series of advanced nasopharyngeal tumor, treated in air and hyperbaric oxygen, respectively. Although it was not truly randomized, the material seems to be comparable in the two groups. The results in patient survival at 2-3 years appear to be better in hyperbaric oxygen. 6 of I3 (46.2%) when compared to 3 of II (27.3%) in air; these results seem encouraging even if they are not significant at this level and with these limited numbers of patients. It is disturbing that three patients were lost to follow-up after the first year in the air series; if these patients were alive at 2-3 years it would remove the difference. The greater incidence of distant metastases in the hyperbaric oxygen group is not surprising with the higher local control rate and, therefore, longer survival. The initial idea that hyperbaric oxygen may increase the incidence of metastases has not been proved correct either in animal studies or in review of randomized patient material from various centers. Some questions can be raised regarding the agressiveness of treatment in air compared with the hyperbaric treatment schedule, since the average time-dose factor (TDF) seems to be ten points lower in air. The choice of the treatment schedule of 9x 500 rad is to be commended since it has been proved conclusively that conventional treatment schedules with hyperbaric oxygen will have relatively little benefit while short treatment schedules of 6-12 fractions in 3-4.5 weeks have been shown to be effective.‘.6 Among other examples, a large randomized study using conventional fractionation by Fletcher et al.,’ in 819
820
Radiation Oncology 0 Biology 0 Physics
July-August
1977, Volume 2, No. 7 and No. 8
REFERENCES I. Chang,
Int. Hyperbaric Congr. Proc. Simon Fraser University, Vancouver, British Columbia, 1974, Vol. II, pp. 650-59. 6. Plenk, H.P.: Present status of hyperbaric radiation therapy. Refresher Course given at RSNA, Dec. 197&
2.
Monograph privately published. 7. R&vCsz, L., L&brand, B.: Variations
3. 4.
5.
C.H., Conley, J.J., Herbert, C., Jr.: Radiotherapy of advanced carcinoma of the oropharyngeal region under hyperbaric oxygen. Am. J. Roentgenol. 117: 509-16, 1973. Fletcher, G.H., Lindberg, R.D., Caderao, J.B., Wharton, J.T.: Hyperbaric oxygen as a radiotherapeutic adjuvant in advanced cancer of the uterine cervix-Cancer 39: 617-623, 1977. Glassburn, J.R., Brady, L.W., Plenk, H.P.: Hyperbaric oxygen in radiation therapy. Cancer 39: 751-765, 1977. Henk, J.M.: Overcoming the oxygen effect: hyperbaric oxygen or protracted fractionation. 5th Int. Hyperbaric Congr. Procs., Vol. II, Vancouver, British Columbia, Simon Fraser University, Vancouver, 1974, pp. 794-801. Nias, A.H.W.: The oxygen enhancement ratio of mammalian cells under different irradiation conditions. 5th
of the oxygen enhancement ratio at different X-ray dose levels and its possible significance. In Advances in Radiation Research Biology and Medicine, ed. by Duplan, J.F. and Chapiro, A. London, Gordon & Breach, 1974, Vol. 3, pp. 1215-1224. 8. Sealy, R.A., Berry, R.J., Ryall, R.D.H., Mills, E.E.D., Sellars, S.L.: The treatment of carcinoma of the nasopharynx in hyperbaric oxygen: An outside assessment. Znt. J. Rad. Oncol. Biol. Phys. 2: 711-714, 1977. 9. Withers, H.R., Scott, O.C.A.: British Empire Cancer Campaign Report, 1964, p. 233.
J
Radiation
Oncology Biol. Phys , 1977, Vol. 2, pp.
819-820.
Pergamon
Press.
Printed
in the U.S.A
0 Editorial
RADIATION
THERAPY
UNDER HYPERBARIC
HENRY P. PLENK, Director.
Radiation
therapy,
Radiation
Hyperbaric
Center.
OXYGEN
M.D.
LDS Hospital. 335 8th Ave.. UT X4143. U.S.A.
Salt Lake City.
oxygen.
the treatment of carcinoma of the cervix, revealed no difference in results. On the other hand, Henk? using a short-fractionation schedule, reported the most impressive data with hyperbaric oxygen to date in the treatment of head and neck cancer. A large randomized trial comparing ten fractions of approximately 400 rad in 3 weeks, with a comparable technique in air, or 30 treatments in air, demonstrated a significant difference in favor of oxygen in the local tumor control rate. While the survivals in the oxygen group were better than those in air, the difference was not significant since a larger number of patients in the air group required salvage surgery, which was successful in many patients; however, when comparing the results in earlier stages of tumors, significant improvement was observed in the oxygen group. The importance of using fewer large fractions in order to take advantage of the maximal oxygen enhancement ratio has been pointed out by Withers and Scott,” RCv&z and Littbrand’ and Nias,’ but has been overlooked in the design of many randomized trials. Only with the use of optimal short-fractionation schedules can we expect to get the greatest benefits from the use of hyperbaric oxygen in radiation therapy. It is hoped that this paper, as well as the experience of Henk,4 Chang et al.,’ Plenk,h Glassburn, Brady and Plenk.7 as well as papers to be published in a forthcoming British Empire Cancer Campaign report, will encourage further randomized studies comparing optimal treatment techniques with hyperbaric oxygen using fewer, larger fractions with optimal treatment techniques in air. While neutrons, radiation sensitizers or hyperthermia may, in the long run, give results equal to, or better than those achieved with hyperbaric oxygen, the full use of hyperbaric oxygen certainly should be pursued, especially by those centers that already have tanks at their disposal, until other available methods can be proven to be superior.
Only a handful of centers in the United States have explored the usefulness of hyperbaric oxygen in the radiation therapy of cancer; very few randomized studies have been conducted in this country. Most studies have come from Great Britain, some from Australia, Canada, South Africa and Japan. The paper by Sealy et al..’ in this issue describes the results in comparable series of advanced nasopharyngeal tumor, treated in air and hyperbaric oxygen, respectively. Although it was not truly randomized, the material seems to be comparable in the two groups. The results in patient survival at 2-3 years appear to be better in hyperbaric oxygen. 6 of I3 (46.2%) when compared to 3 of II (27.3%) in air; these results seem encouraging even if they are not significant at this level and with these limited numbers of patients. It is disturbing that three patients were lost to follow-up after the first year in the air series; if these patients were alive at 2-3 years it would remove the difference. The greater incidence of distant metastases in the hyperbaric oxygen group is not surprising with the higher local control rate and, therefore, longer survival. The initial idea that hyperbaric oxygen may increase the incidence of metastases has not been proved correct either in animal studies or in review of randomized patient material from various centers. Some questions can be raised regarding the agressiveness of treatment in air compared with the hyperbaric treatment schedule, since the average time-dose factor (TDF) seems to be ten points lower in air. The choice of the treatment schedule of 9x 500 rad is to be commended since it has been proved conclusively that conventional treatment schedules with hyperbaric oxygen will have relatively little benefit while short treatment schedules of 6-12 fractions in 3-4.5 weeks have been shown to be effective.‘.6 Among other examples, a large randomized study using conventional fractionation by Fletcher et al.,’ in 819
820
Radiation Oncology 0 Biology 0 Physics
July-August
1977, Volume 2, No. 7 and No. 8
REFERENCES I. Chang,
Int. Hyperbaric Congr. Proc. Simon Fraser University, Vancouver, British Columbia, 1974, Vol. II, pp. 650-59. 6. Plenk, H.P.: Present status of hyperbaric radiation therapy. Refresher Course given at RSNA, Dec. 197&
2.
Monograph privately published. 7. R&vCsz, L., L&brand, B.: Variations
3. 4.
5.
C.H., Conley, J.J., Herbert, C., Jr.: Radiotherapy of advanced carcinoma of the oropharyngeal region under hyperbaric oxygen. Am. J. Roentgenol. 117: 509-16, 1973. Fletcher, G.H., Lindberg, R.D., Caderao, J.B., Wharton, J.T.: Hyperbaric oxygen as a radiotherapeutic adjuvant in advanced cancer of the uterine cervix-Cancer 39: 617-623, 1977. Glassburn, J.R., Brady, L.W., Plenk, H.P.: Hyperbaric oxygen in radiation therapy. Cancer 39: 751-765, 1977. Henk, J.M.: Overcoming the oxygen effect: hyperbaric oxygen or protracted fractionation. 5th Int. Hyperbaric Congr. Procs., Vol. II, Vancouver, British Columbia, Simon Fraser University, Vancouver, 1974, pp. 794-801. Nias, A.H.W.: The oxygen enhancement ratio of mammalian cells under different irradiation conditions. 5th
of the oxygen enhancement ratio at different X-ray dose levels and its possible significance. In Advances in Radiation Research Biology and Medicine, ed. by Duplan, J.F. and Chapiro, A. London, Gordon & Breach, 1974, Vol. 3, pp. 1215-1224. 8. Sealy, R.A., Berry, R.J., Ryall, R.D.H., Mills, E.E.D., Sellars, S.L.: The treatment of carcinoma of the nasopharynx in hyperbaric oxygen: An outside assessment. Znt. J. Rad. Oncol. Biol. Phys. 2: 711-714, 1977. 9. Withers, H.R., Scott, O.C.A.: British Empire Cancer Campaign Report, 1964, p. 233.