Skip to main content
PMC home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1973 Mar;27(3):253–267. doi: 10.1038/bjc.1973.30

Glioblastoma Multiforme: A Controlled Trial to Assess the Value of Specific Active Immunotherapy in Patients Treated by Radical Surgery and Radiotherapy

H J G Bloom, M J Peckham, A E Richardson, P A Alexander, P M Payne
PMCID: PMC2008773  PMID: 4348472

Abstract

The results are reported of a randomized prospective clinical trial carried out to assess the value of specific active immunotherapy using irradiated autologous tumour cells in patients with glioblastoma multiforme treated by radical surgery and post-operative irradiation. The results in 62 patients show no statistically significant difference in survival between the group receiving adjuvant autologous tumour cells and those treated with surgery and radiotherapy alone. All 27 patients receiving tumour cells were dead at 30 months, whereas 7 of the 35 controls were alive at this time. The results were considered sufficiently discouraging to abandon the trial at this stage on the grounds that there was sufficient evidence in this study that the administration of irradiated autologous cells was of no benefit to patients with high grade astrocytomata.

Full text

PDF
253

Selected References

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

  1. Anderson J. M., De Sousa M. A., Halnan K. E., Kelly F., Hannah G. Assessment of immunization by autotransplantation of human cancer. Br J Surg. 1970 Aug;57(8):557–561. doi: 10.1002/bjs.1800570802. [DOI] [PubMed] [Google Scholar]
  2. BLACK M. M., OPLER S. R., SPEER F. D. Structural representations of tumor-host relationships in gastric carcinoma. Surg Gynecol Obstet. 1956 May;102(5):599–603. [PubMed] [Google Scholar]
  3. Bloch M., Bloom H. J., Penman J., Walsh L. Observations on patients with cerebral astrocytoma (glioblastoma multiforme) treated by irradiation under whole-body hypothermia. Br J Cancer. 1966 Dec;20(4):722–728. doi: 10.1038/bjc.1966.83. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bloom H. J., Richardson W. W., Field J. R. Host resistance and survival in carcinoma of breast: a study of 104 cases of medullary carcinoma in a series of 1,411 cases of breast cancer followed for 20 years. Br Med J. 1970 Jul 25;3(5716):181–188. doi: 10.1136/bmj.3.5716.181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. CRAIG W. M., DODGE H. W., Jr, SVIEN H. J. Brain tumors; practical approach and classification. Minn Med. 1957 Jul;40(7):471–476. [PubMed] [Google Scholar]
  6. Currie G. A., Basham C. Serum mediated inhibition of the immunological reactions of the patient to his own tumour: a possible role for circulating antigen. Br J Cancer. 1972 Dec;26(6):427–438. doi: 10.1038/bjc.1972.59. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Currie G. A. Eighty years of immunotherapy: a review of immunological methods used for the treatment of human cancer. Br J Cancer. 1972 Jun;26(3):141–153. doi: 10.1038/bjc.1972.21. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Delpech B., Delpech A., Clément J., Laumonier R. Etude immunochimique et immunologique des tumeurs du cerveau humain. Int J Cancer. 1972 Mar 15;9(2):374–382. doi: 10.1002/ijc.2910090216. [DOI] [PubMed] [Google Scholar]
  9. EARLE K. M., RENTSCHLER E. H., SNODGRASS S. R. Primary intracranial neoplasms; prognosis and classification of 513 varified cases. J Neuropathol Exp Neurol. 1957 Jul;16(3):321–331. doi: 10.1097/00005072-195707000-00003. [DOI] [PubMed] [Google Scholar]
  10. Edland R. W., Javid M., Ansfield F. J. Glioblastoma multiforme. An analysis of the results of postoperative radiotherapy alone versus radiotherapy and concomitant 5-fluorouracil. (A prospective randomized study of 32 cases). Am J Roentgenol Radium Ther Nucl Med. 1971 Feb;111(2):337–342. doi: 10.2214/ajr.111.2.337. [DOI] [PubMed] [Google Scholar]
  11. FOLEY E. J. Antigenic properties of methylcholanthrene-induced tumors in mice of the strain of origin. Cancer Res. 1953 Dec;13(12):835–837. [PubMed] [Google Scholar]
  12. FRANKEL S. A., GERMAN W. J. Glioblastoma multiforme; review of 219 cases with regard to natural history, pathology, diagnostic methods, and treatment. J Neurosurg. 1958 Sep;15(5):489–503. doi: 10.3171/jns.1958.15.5.0489. [DOI] [PubMed] [Google Scholar]
  13. Fairley G. H. Immunity to malignant disease in man. Br Med J. 1969 May 24;2(5655):467–473. doi: 10.1136/bmj.2.5655.467. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. GOWANS J. L. The recirculation of lymphocytes from blood to lymph in the rat. J Physiol. 1959 Apr 23;146(1):54–69. doi: 10.1113/jphysiol.1959.sp006177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. HADDOW A., ALEXANDER P. AN IMMUNOLOGICAL METHOD OF INCREASING THE SENSITIVITY OF PRIMARY SARCOMAS TO LOCAL IRRADIATION WITH X RAYS. Lancet. 1964 Feb 29;1(7331):452–457. doi: 10.1016/s0140-6736(64)90793-7. [DOI] [PubMed] [Google Scholar]
  16. HITCHCOCK E., SATO R. TREATMENT OF MALIGNANT GLIOMATA. J Neurosurg. 1964 Jun;21:497–505. doi: 10.3171/jns.1964.21.6.0497. [DOI] [PubMed] [Google Scholar]
  17. Hamlin I. M. Possible host resistance in carcinoma of the breast: a histological study. Br J Cancer. 1968 Sep;22(3):383–401. doi: 10.1038/bjc.1968.47. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hatcher V. B., MacPherson C. F. Studies on brain antigens. 3. Purification and characterization of a water-soluble bovine antigen specific for nervous tissue (alpha-BASNT). J Immunol. 1970 Mar;104(3):633–640. [PubMed] [Google Scholar]
  19. Hellström I. E., Hellström K. E., Pierce G. E., Bill A. H. Demonstration of cell-bound and humoral immunity against neuroblastoma cells. Proc Natl Acad Sci U S A. 1968 Aug;60(4):1231–1238. doi: 10.1073/pnas.60.4.1231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Hellström K. E., Hellström I. Immunological enhancement as studied by cell culture techniques. Annu Rev Microbiol. 1970;24:373–398. doi: 10.1146/annurev.mi.24.100170.002105. [DOI] [PubMed] [Google Scholar]
  21. Hopewell J. W., Wright E. A. The importance of implantation site in cerebral carcinogenesis in rats. Cancer Res. 1969 Nov;29(11):1927–1931. [PubMed] [Google Scholar]
  22. Ikonopisov R. L., Lewis M. G., Hunter-Craig I. D., Bodenham D. C., Phillips T. M., Cooling C. I., Proctor J., Fairley G. H., Alexander P. Autoimmunization with irradiated tumour cells in human malignant melanoma. Br Med J. 1970 Jun 27;2(5712):752–754. doi: 10.1136/bmj.2.5712.752. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. JOHNSON H. A., HAYMAKER W. E., RUBINI J. R., FLIEDNER T. M., BOND V. P., CRONKITE E. P., HUGHES W. L. A radioautographic study of a human brain and glioblastoma multiforme after the in vivo uptake of tritiated thymidine. Cancer. 1960 May-Jun;13:636–642. doi: 10.1002/1097-0142(196005/06)13:3<636::aid-cncr2820130328>3.0.co;2-r. [DOI] [PubMed] [Google Scholar]
  24. Jelsma R., Bucy P. C. Glioblastoma multiforme: its treatment and some factors effecting survival. Arch Neurol. 1969 Feb;20(2):161–171. doi: 10.1001/archneur.1969.00480080061007. [DOI] [PubMed] [Google Scholar]
  25. Klein G., Clifford P., Klein E., Smith R. T., Minowada J., Kourilsky F. M., Burchenal J. H. Membrane immunofluorescence reactions of Burkitt lymphoma cells from biopsy specimens and tissue cultures. J Natl Cancer Inst. 1967 Nov;39(5):1027–1044. [PubMed] [Google Scholar]
  26. LAWRENCE J. H., TOBIAS C. A., BORN J. L., WANGCC, LINFOOT J. H. Heavy-particle irradiation in neoplastic and neurologic disease. J Neurosurg. 1962 Sep;19:717–722. doi: 10.3171/jns.1962.19.9.0717. [DOI] [PubMed] [Google Scholar]
  27. Law L. W., Appella E., Wright P. W., Strober S. Immunologic enhancement of allogeneic tumor growth with soluble histocompatibility-2 antigens. Proc Natl Acad Sci U S A. 1971 Dec;68(12):3078–3082. doi: 10.1073/pnas.68.12.3078. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Levy N. L., Mahaley M. S., Jr, Day E. D. In vitro demonstration of cell-mediated immunity to human brain tumors. Cancer Res. 1972 Mar;32(3):477–482. [PubMed] [Google Scholar]
  29. Lewis M. G., Ikonopisov R. L., Nairn R. C., Phillips T. M., Fairley G. H., Bodenham D. C., Alexander P. Tumour-specific antibodies in human malignant melanoma and their relationship to the extent of the disease. Br Med J. 1969 Sep 6;3(5670):547–552. doi: 10.1136/bmj.3.5670.547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Lim R., Kluskens L. Immunological specificity of astrocytoma antigens. Cancer Res. 1972 Aug;32(8):1667–1670. [PubMed] [Google Scholar]
  31. MATSUKADO Y., MACCARTY C. S., KERNOHAN J. W. The growth of glioblastoma multiforme (astrocytomas, grades 3 and 4) in neurosurgical practice. J Neurosurg. 1961 Sep;18:636–644. doi: 10.3171/jns.1961.18.5.0636. [DOI] [PubMed] [Google Scholar]
  32. Mahaley M. S., Jr, Day E. D. Immunological studies of human gliomas. J Neurosurg. 1965 Oct;23(4):363–370. doi: 10.3171/jns.1965.23.4.0363. [DOI] [PubMed] [Google Scholar]
  33. Mahaley M. S., Jr Immunological considerations and the malignant glioma problem. Clin Neurosurg. 1968;15:175–189. doi: 10.1093/neurosurgery/15.cn_suppl_1.175. [DOI] [PubMed] [Google Scholar]
  34. Mahaley M. S., Jr Immunological studies with human gliomas. J Neurosurg. 1971 Mar;34(3):458–459. doi: 10.3171/jns.1971.34.3.0458. [DOI] [PubMed] [Google Scholar]
  35. Martin R. F., Beckwith J. B. Lymphoid infiltrates in neuroblastomas: their occurrence and prognostic significance. J Pediatr Surg. 1968 Feb;3(1):161–164. doi: 10.1016/0022-3468(68)91005-1. [DOI] [PubMed] [Google Scholar]
  36. Morton D. L., Malmgren R. A., Holmes E. C., Ketcham A. S. Demonstration of antibodies against human malignant melanoma by immunofluorescence. Surgery. 1968 Jul;64(1):233–240. [PubMed] [Google Scholar]
  37. OLD L. J., BOYSE E. A. IMMUNOLOGY OF EXPERIMENTAL TUMORS. Annu Rev Med. 1964;15:167–186. doi: 10.1146/annurev.me.15.020164.001123. [DOI] [PubMed] [Google Scholar]
  38. PREHN R. T., MAIN J. M. Immunity to methylcholanthrene-induced sarcomas. J Natl Cancer Inst. 1957 Jun;18(6):769–778. [PubMed] [Google Scholar]
  39. Paterson P. Y. Experimental allergic encephalomyelitis and autoimmune disease. Adv Immunol. 1966;5:131–208. doi: 10.1016/s0065-2776(08)60273-4. [DOI] [PubMed] [Google Scholar]
  40. ROTH J. G., ELVIDGE A. R. Glioblastoma multiforme: a clinical survey. J Neurosurg. 1960 Jul;17:736–750. doi: 10.3171/jns.1960.17.4.0736. [DOI] [PubMed] [Google Scholar]
  41. Ridley A., Cavanagh J. B. Lymphocytic infiltration in gliomas: evidence of possible host resistance. Brain. 1971;94(1):117–124. doi: 10.1093/brain/94.1.117. [DOI] [PubMed] [Google Scholar]
  42. TAVERAS J. M., THOMPSON H. G., Jr, POOL J. L. Should we treat glioblastoma multiforme? A study of survival in 425 cases. Am J Roentgenol Radium Ther Nucl Med. 1962 Mar;87:473–479. [PubMed] [Google Scholar]
  43. Trouillas P. Carcino-fetal antigen in glial tumours. Lancet. 1971 Sep 4;2(7723):552–552. doi: 10.1016/s0140-6736(71)90478-8. [DOI] [PubMed] [Google Scholar]
  44. Vaage J. Concomitant immunity and specific depression of immunity by residual or reinjected syngeneic tumor tissue. Cancer Res. 1971 Nov;31(11):1655–1662. [PubMed] [Google Scholar]
  45. WOLF A., COWEN D., STEWART W. B. Glioblastoma with extraneural metastasis by way of a ventriculopleural anastomosis. Trans Am Neurol Assoc. 1954;13(79TH):140–142. [PubMed] [Google Scholar]
  46. Wakamatsu T., Matsuo T., Kawano S., Teramoto S., Matsumura H. Glioblastoma with extracranial metastasis through ventriculopleural shunt. Case report. J Neurosurg. 1971 May;34(5):697–701. doi: 10.3171/jns.1971.34.5.0697. [DOI] [PubMed] [Google Scholar]
  47. Wickremesinghe H. R., Yates P. O. Immunological properties of neoplastic neural tissues. Br J Cancer. 1971 Dec;25(4):711–720. doi: 10.1038/bjc.1971.86. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Wilson C. B., Hoshino T. Current trends in the chemotherapy of brain tumors with special reference to glioblastomas. J Neurosurg. 1969 Dec;31(6):589–603. doi: 10.3171/jns.1969.31.6.0589. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES