Journal of Radiation Oncology

, Volume 6, Issue 2, pp 109–115 | Cite as

Low-dose total body irradiation: an overlooked cancer immunotherapy technique

Review

Abstract

Low-dose total body irradiation (LD-TBI) has been shown to be an effective therapy for patients with hematologic malignancies. The application of this method has fallen out of favor as newer systemic therapies have been developed. Nevertheless, for management of many of these hematologic malignancies, no prospective randomized trial has shown that any other treatment is unequivocally superior to LD-TBI. The precise mechanism of action is uncertain but it is believed by some to be at least partly immunologically mediated. In this review, we shall discuss the clinical data on this method along with some new potential applications. We also discuss some of the potential immunological mechanisms behind LD-TBI and consider future possibilities.

Keywords

TBI Total body irradiation Cancer immunotherapy 

References

  1. 1.
    Safwat A (2000) The immunobiology of low-dose total-body irradiation: more questions than answers. Radiat Res 153:599–604CrossRefPubMedGoogle Scholar
  2. 2.
    Johnson RE (1966) Evaluation of fractionated total-body irradiation in patients with leukemia and disseminated lymphomas. Radiology 86:1085–1089CrossRefPubMedGoogle Scholar
  3. 3.
    Qasim MM (1979) Total body irradiation as a primary therapy in non-Hodgkin lymphoma. Clin Radiol 30:287–286CrossRefPubMedGoogle Scholar
  4. 4.
    Chaffey JT, Rosenthal DS, Pinkus F, Hellman S (1975) Advanced lymphosarcoma treated by total body irradiation. Br J Cancer 31(SUPPL 2):441–449Google Scholar
  5. 5.
    Hoppe RT, Kushlan P, Kaplan HS, Rosenberg SA, Brown BW (1981) The treatment of advanced stage favorable histology non-Hodgkin’s lymphoma: a preliminary report of a randomized trial comparing single agent chemotherapy, combination chemotherapy, and whole body irradiation. Blood 58:592–598PubMedGoogle Scholar
  6. 6.
    Wang B, Li B, Dai Z et al (2014) Low-dose splenic radiation inhibits liver tumor development of rats through functional changes in CD4+CD25+Treg cells. Int J Biochem Cell Biol 55:98–108CrossRefPubMedGoogle Scholar
  7. 7.
    Dreyling M, Ghielmini M, Marcus R et al (2011) Newly diagnosed and relapsed follicular lymphoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 22:vi59–vi63CrossRefPubMedGoogle Scholar
  8. 8.
    Lowry L, Smith P, Qian W et al (2011) Reduced dose radiotherapy for local control in non-Hodgkin lymphoma: a randomised phase III trial. Radiother Oncol 100:86–92CrossRefPubMedGoogle Scholar
  9. 9.
    Kamstrup MR, Gniadecki R, Iversen L et al (2015) Low-dose (10-Gy) total skin electron beam therapy for cutaneous T-cell lymphoma: an open clinical study and pooled data analysis. Int J Radiat Oncol Biol Phys 92(1):138–143CrossRefPubMedGoogle Scholar
  10. 10.
    Hoppe RT, Harrison C, Tavallaee M et al (2015) Low-dose total skin electron beam therapy as an effective modality to reduce disease burden in patients with mycosis fungoides: results of a pooled analysis from 3 phase-II clinical trials. J Am Acad Dermatol 72(2):286–292CrossRefPubMedGoogle Scholar
  11. 11.
    Haas RL (2009) Low dose radiotherapy in indolent lymphomas, enough is enough. Hematol Oncol 27(2):71–81CrossRefPubMedGoogle Scholar
  12. 12.
    Ganem G, Cartron G, Girinsky T, Haas RL, Cosset JM, Solal-Celigny P (2010) Localized low-dose radiotherapy for follicular lymphoma: history, clinical results, mechanisms of action, and future outlooks. Int J Radiat Oncol Biol Phys 78(4):975–982CrossRefPubMedGoogle Scholar
  13. 13.
    Ganem G, Lambin P, Socié G et al (1994) Potential role for low dose limited-field radiation therapy (2 x 2 grays) in advanced low-grade non-Hodgkin’s lymphomas. Hematol Oncol 12(1):1–8CrossRefPubMedGoogle Scholar
  14. 14.
    Girinsky T, Paumier A, Ferme C et al (2012) Low-dose radiation treatment in pulmonary mucosa-associated lymphoid tissue lymphoma: a plausible approach? A single-institution experience in 10 patients. Int J Radiat Oncol Biol Phys 83(3):e385–e389CrossRefPubMedGoogle Scholar
  15. 15.
    Choi NC, Timothy AR, Kaufman SD, Carey RW, Aisenberg AC (1979) Low dose fractionated whole body irradiation in the treatment of advanced non-Hodgkin’s lymphoma. Cancer 43:1636–1642CrossRefPubMedGoogle Scholar
  16. 16.
    Safwat A, Bayoumy Y, El-Sharkawy N, Shaaban K, Mansour O, Kamel A (2003) The potential palliative role and possible immune modulatory effects of low-dose total body irradiation in relapsed or chemoresistant non-Hodgkin’s lymphoma. Radiother Oncol 69:33–36CrossRefPubMedGoogle Scholar
  17. 17.
    Cuttler JM, Pollycove M (2003) Can cancer be treated with low doses of radiation? J Am Phys Surg 8:108–111Google Scholar
  18. 18.
    Oakley PA (2015) Is use of radiation Hormesis the missing link to a better cancer treatment? Journal of Cancer Therapy 6:601–605CrossRefGoogle Scholar
  19. 19.
    Song KH, Kim MH, Kang SM et al (2015) Analysis of immune cell populations and cytokine profiles in murine splenocytes exposed to whole-body low-dose irradiation. Int J Radiat Biol 23:1–9 [Epub ahead of print]Google Scholar
  20. 20.
    Bayoumi Y, Radwan A (2015) Low dose total body irradiation for relapsed low grade non-Hodgkin’s lymphoma: experience of National Cancer Institute, Cairo. Journal of Cancer Therapy 6:25–33CrossRefGoogle Scholar
  21. 21.
    Cao M, Cabrera R, Xu Y, Liu C, Nelson D (2011) Different radiosensitivity of CD4+CD25+ regulatory T cells and effector T cells to low dose gamma irradiation in vitro. Int J Radiat Biol 87(1):71–80CrossRefPubMedGoogle Scholar
  22. 22.
    Welsh JS (2004) Waldenstrom’s Macroglobulinemia treated with fractionated low-dose total body irradiation. Case Rep Clin Pract Rev 5:CS425–CS431Google Scholar
  23. 23.
    Chaffey JT, Rosenthal DS, Moloney WC, Hellman S (1976) Total body irradiation as treatment for lymphosarcoma. Int J Radiat Oncol Biol Phys 1(5–6):399–405CrossRefPubMedGoogle Scholar
  24. 24.
    Brereton HD, Young RC, Longo DL et al (1979) A comparison between combination chemotherapy and total body irradiation plus combination chemotherapy in non-Hodgkin’s lymphoma. Cancer 43:2227–2231CrossRefPubMedGoogle Scholar
  25. 25.
    Anonymous (1981) British National Lymphoma Investigation Report: a prospective comparison of combination chemotherapy with total body irradiation in the treatment of advanced non-Hodgkin’s lymphoma. Clin Oncol 7:193–200Google Scholar
  26. 26.
    Meerwaldt JH, Carde P, Burgers JM et al (1991) Low dose total body irradiation versus combination chemotherapy for lymphomas with follicular growth pattern. Int J Radiat Oncol Biol Phys 21:1167–1172CrossRefPubMedGoogle Scholar
  27. 27.
    Weick JK, Antunez A, Kraus TA (1983) The combined modality therapy of diffuse histology non-Hodgkin’s lymphoma with CHOP and total body irradiation. Int J Radiat Oncol Biol Phys 9:1205–1207CrossRefPubMedGoogle Scholar
  28. 28.
    Richaud PM, Soubeyran P, Eghbali H et al (1998) Place of low-dose total body irradiation in the treatment of localized follicular non-Hodgkin’s lymphoma: results of a pilot study. Int J Radiat Oncol Biol Phys 40(2):387–390CrossRefPubMedGoogle Scholar
  29. 29.
    Johnson RE, Canellos GP, Young RC, Chabner BA, DeVita VT (1978) Chemotherapy (cyclophosphamide, vincristine, and prednisone) versus radiotherapy (total body irradiation) for stage III-IV poorly differentiated lymphocytic lymphoma. Cancer Treat Rep 62:321–325PubMedGoogle Scholar
  30. 30.
    Travis LB, Weeks J, Curtis RE et al (1996) Leukemia following low-dose total body irradiation and chemotherapy for non-Hodgkin’s lymphoma. J Clin Oncol 14:565–571CrossRefPubMedGoogle Scholar
  31. 31.
    Ellis M, Lishner M (1993) Second malignancies following treatment in non-Hodgkin’s lymphoma. Leuk Lymphoma 9:337–342CrossRefPubMedGoogle Scholar
  32. 32.
    Kollmannsberger C, Hartmann JT, Kanz L, Bokemeyer C (1998) Risk of secondary myeloid leukemia and myelodysplastic syndrome following standard-dose chemotherapy or high-dose chemotherapy with stem cell support in patients with potentially curable malignancies. J Cancer Res Clin Oncol 124(3–4):207–214CrossRefPubMedGoogle Scholar
  33. 33.
    Thomas A, Mailankody S, Korde N, Kristinsson SY, Turesson I, Landgren O (2012) Second malignancies after multiple myeloma: from 1960s to 2010s. Blood 119(12):2731–2737CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Tubiana M (2009) Can we reduce the incidence of second primary malignancies occurring after radiotherapy? A critical review. Radiother Oncol 91:4–15CrossRefPubMedGoogle Scholar
  35. 35.
    Mendenhall NP, Noyes WD, Million RR (1989) Total body irradiation for stage II-IV non-Hodgkin’s lymphoma: ten-year follow-up. J Clin Oncol 7:67–74CrossRefPubMedGoogle Scholar
  36. 36.
    Dobbs HJ, Barrett A, Rostom AY et al (1981) Total body irradiation in advanced non-Hodgkin’s lymphoma. Br J Radiol 54:878–881CrossRefPubMedGoogle Scholar
  37. 37.
    Lybeert ML, Meerwaldt JH, Deneve W (1987) Long-term results of low dose total body irradiation for advanced non-Hodgkin lymphoma. Int J Radiat Oncol Biol Phys 13:1167–1172CrossRefPubMedGoogle Scholar
  38. 38.
    Fourquet A, Teillaud JL, Lando D et al (1993) Effects of low dose total body irradiation and recombinant human interlukin-2 in mice. Radiother Oncol 26:219–225CrossRefPubMedGoogle Scholar
  39. 39.
    Yonkosky DM, Feldman MI, Cathcart ES, Kim S (1978) Improvement of in-vitro mitogen proliferative responses in non-Hodgkin’s lymphoma patients exposed to fractionated total body irradiation. Cancer 42:1204–1210CrossRefPubMedGoogle Scholar
  40. 40.
    Safwat A (2000) The role of low-dose total body irradiation in treatment of NHL: a new look at an old method. Radiother Oncol 56:1–8CrossRefPubMedGoogle Scholar
  41. 41.
    Pollycove M (2007) Radiobiological basis of low-dose irradiation in prevention and therapy of cancer. Dose-Response 5(1):26–38CrossRefGoogle Scholar
  42. 42.
    Nowosielska EM, Cheda A, Wrembel-Wargocka J, Janiak MK (2010) Immunological mechanism of the low-dose radiation-induced suppression of cancer metastases in a mouse model. Dose Response 8(2):209–226CrossRefGoogle Scholar
  43. 43.
    Safwat A, Aggerholm N, Roitt I, Overgaard J, Hokland M (2003) Low-dose total body irradiation augments the therapeutic effect of interleukin-2 in a mouse model for metastatic malignant melanoma. J Exp Ther Oncol 3:161–168CrossRefPubMedGoogle Scholar
  44. 44.
    Hosoi Y, Sakamoto K (1993) Suppressive effect of low dose total body irradiation on lung metastasis: dose dependency and effective period. Radiother Oncol 26:177–179CrossRefPubMedGoogle Scholar
  45. 45.
    Hosoi Y (2006) Antitumor effects by low dose total body irradiation. [Article in Japanese with English abstract] Yakugaku Zasshi 126(10):841–848CrossRefPubMedGoogle Scholar
  46. 46.
    Safwat A, Schmidt H, Bastholt L et al (2005) A phase II trial of low-dose total body irradiation and subcutaneous interleukin-2 in metastatic melanoma. Radiother Oncol 77:143–147CrossRefPubMedGoogle Scholar
  47. 47.
    Sakamoto K, Myogin M, Hosoi Y (1997) Fundamental and clinical studies on cancer control with total or upper half body irradiation. J Jpn Soc Ther Radiol Oncol 16:161–175Google Scholar
  48. 48.
    Song KH, Kim MH, Kang SM et al (2015) Analysis of immune cell populations and cytokine profiles in murine splenocytes exposed to whole-body low-dose irradiation. Int J Radiat Biol 91(10):795–803CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Alec M. Block
    • 1
  • Scott R. Silva
    • 1
  • James S. Welsh
    • 1
  1. 1.Stritch School of Medicine, Department of Radiation OncologyLoyola University of ChicagoMaywoodUSA

Personalised recommendations