Display options
Cite
Crocenzi T, Cottam B, Newell P, et al. A hypofractionated radiation regimen avoids the lymphopenia associated with neoadjuvant chemoradiation therapy of borderline resectable and locally advanced pancreatic adenocarcinoma. J Immunother Cancer. 2016;4:45doi: 10.1186/s40425-016-0149-6.
Crocenzi, T., Cottam, B., Newell, P., Wolf, R. F., Hansen, P. D., Hammill, C., Solhjem, M. C., To, Y. Y., Greathouse, A., Tormoen, G., Jutric, Z., Young, K., Bahjat, K. S., Gough, M. J., & Crittenden, M. R. (2016). A hypofractionated radiation regimen avoids the lymphopenia associated with neoadjuvant chemoradiation therapy of borderline resectable and locally advanced pancreatic adenocarcinoma. Journal for immunotherapy of cancer, 445. https://doi.org/10.1186/s40425-016-0149-6
Crocenzi, Todd, et al. "A hypofractionated radiation regimen avoids the lymphopenia associated with neoadjuvant chemoradiation therapy of borderline resectable and locally advanced pancreatic adenocarcinoma." Journal for immunotherapy of cancer vol. 4 (2016): 45. doi: https://doi.org/10.1186/s40425-016-0149-6
Crocenzi T, Cottam B, Newell P, Wolf RF, Hansen PD, Hammill C, Solhjem MC, To YY, Greathouse A, Tormoen G, Jutric Z, Young K, Bahjat KS, Gough MJ, Crittenden MR. A hypofractionated radiation regimen avoids the lymphopenia associated with neoadjuvant chemoradiation therapy of borderline resectable and locally advanced pancreatic adenocarcinoma. J Immunother Cancer. 2016 Aug 16;4:45. doi: 10.1186/s40425-016-0149-6. eCollection 2016. PMID: 27532020; PMCID: PMC4986363.
Copy Download .nbib Format: NLM
Share it on

J Immunother Cancer. 2016 Aug 16;4:45. doi: 10.1186/s40425-016-0149-6. eCollection 2016.

A hypofractionated radiation regimen avoids the lymphopenia associated with neoadjuvant chemoradiation therapy of borderline resectable and locally advanced pancreatic adenocarcinoma.

Journal for immunotherapy of cancer

Todd Crocenzi, Benjamin Cottam, Pippa Newell, Ronald F Wolf, Paul D Hansen, Chet Hammill, Matthew C Solhjem, Yue-Yun To, Amy Greathouse, Garth Tormoen, Zeljka Jutric, Kristina Young, Keith S Bahjat, Michael J Gough, Marka R Crittenden

Affiliations

  1. Earle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical Center, 4805 NE Glisan St, Portland, OR 97213 USA.
  2. Earle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical Center, 4805 NE Glisan St, Portland, OR 97213 USA ; The Oregon Clinic, Portland, OR 97213 USA ; Providence Hepatobiliary and Pancreatic Cancer Program, Providence Portland Medical Center, 4805 NE Glisan St, Portland, OR 97213 USA.
  3. The Oregon Clinic, Portland, OR 97213 USA ; Providence Hepatobiliary and Pancreatic Cancer Program, Providence Portland Medical Center, 4805 NE Glisan St, Portland, OR 97213 USA.
  4. The Oregon Clinic, Portland, OR 97213 USA.
  5. Oregon Health and Sciences University, Sam Jackson Parkway, Portland, OR USA.
  6. Providence Hepatobiliary and Pancreatic Cancer Program, Providence Portland Medical Center, 4805 NE Glisan St, Portland, OR 97213 USA.
  7. Earle A. Chiles Research Institute, Robert W. Franz Cancer Center, Providence Portland Medical Center, 4805 NE Glisan St, Portland, OR 97213 USA ; The Oregon Clinic, Portland, OR 97213 USA.

PMID: 27532020 PMCID: PMC4986363 DOI: 10.1186/s40425-016-0149-6

Abstract

BACKGROUND: Preclinical studies have shown synergy between radiation therapy and immunotherapy. However, in almost all preclinical models, radiation is delivered in single doses or short courses of high doses (hypofractionated radiation). By contrast in most clinical settings, radiation is delivered as standard small daily fractions of 1.8-2 Gy to achieve total doses of 50-54 Gy (fractionated radiation). We do not yet know the optimal dose and scheduling of radiation for combination with chemotherapy and immunotherapy.

METHODS: To address this, we analyzed the effect of neoadjuvant standard fractionated and hypofractionated chemoradiation on immune cells in patients with locally advanced and borderline resectable pancreatic adenocarcinoma.

RESULTS: We found that standard fractionated chemoradiation resulted in a significant and extended loss of lymphocytes that was not explained by a lack of homeostatic cytokines or response to cytokines. By contrast, treatment with hypofractionated radiation therapy avoided the loss of lymphocytes associated with conventional fractionation.

CONCLUSION: Hypofractionated neoadjuvant chemoradiation is associated with reduced systemic loss of T cells.

TRIAL REGISTRATION: ClinicalTrials.gov NCT01342224, April 21, 2011; NCT01903083, July 2, 2013.

Keywords: Chemotherapy; Fractionation; Gemcitabine; Homeostatic repopulation; IL-15; IL-7; Immunotherapy; Lymphocytes; Lymphodepletion; Radiation

References

  1. Cancer. 2015 Apr 1;121(7):1128-37 - PubMed
  2. Cancer Invest. 2013 Feb;31(2):140-4 - PubMed
  3. Clin Cancer Res. 2013 Dec 1;19(23):6585-96 - PubMed
  4. Cancer Immunol Res. 2013 Jul;1(1):32-42 - PubMed
  5. J Exp Med. 2005 Oct 3;202(7):907-12 - PubMed
  6. PLoS One. 2013 Jul 25;8(7):e69527 - PubMed
  7. Head Neck. 2014 Dec;36(12):1747-53 - PubMed
  8. Cancer Immunol Res. 2015 Apr;3(4):399-411 - PubMed
  9. J Clin Invest. 2002 Jul;110(2):185-92 - PubMed
  10. Clin Cancer Res. 2005 Jan 15;11(2 Pt 1):728-34 - PubMed
  11. N Engl J Med. 2011 May 12;364(19):1817-25 - PubMed
  12. Am J Clin Oncol. 2015 Jun;38(3):259-65 - PubMed
  13. Int J Radiat Oncol Biol Phys. 2013 Jul 1;86(3):516-22 - PubMed
  14. J Immunother. 2010 Oct;33(8):798-809 - PubMed
  15. Thorax. 1980 Jul;35(7):500-5 - PubMed
  16. Ann Oncol. 2013 Jan;24(1):75-83 - PubMed
  17. Cancer Immunol Immunother. 2013 Feb;62(2):203-16 - PubMed
  18. Sci Transl Med. 2012 Jun 6;4(137):137ra74 - PubMed
  19. N Engl J Med. 2013 Oct 31;369(18):1691-703 - PubMed
  20. Ann Surg Oncol. 2009 Jul;16(7):1727-33 - PubMed
  21. J Natl Compr Canc Netw. 2015 Oct;13(10):1225-31 - PubMed
  22. J Clin Oncol. 2012 Jun 10;30(17 ):2046-54 - PubMed
  23. Cancer Res. 2013 Feb 1;73(3):1128-41 - PubMed
  24. J Exp Med. 2000 Aug 21;192(4):557-64 - PubMed
  25. Nat Rev Immunol. 2012 Feb 17;12(3):191-200 - PubMed
  26. J Clin Invest. 1976 Oct;58(4):803-14 - PubMed
  27. PLoS One. 2016 Jun 09;11(6):e0157164 - PubMed
  28. J Immunol. 2001 Nov 15;167(10):5664-8 - PubMed
  29. Clin Immunol. 2004 Mar;110(3):206-21 - PubMed
  30. Cancer Immunol Res. 2015 Apr;3(4):345-55 - PubMed
  31. Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):3031-6 - PubMed
  32. Oncoimmunology. 2014 Jan 1;3(1):e27357 - PubMed
  33. J Clin Oncol. 2005 Apr 1;23(10):2346-57 - PubMed
  34. CA Cancer J Clin. 2015 Jan-Feb;65(1):5-29 - PubMed
  35. Cancer Invest. 1999;17(1):56-72 - PubMed
  36. Radiology. 1976 Jan;118(1):201-10 - PubMed
  37. J Exp Med. 2013 Oct 21;210(11):2435-66 - PubMed
  38. Am J Clin Oncol. 2007 Dec;30(6):637-44 - PubMed
  39. Immunology. 2005 Jan;114(1):11-22 - PubMed
  40. Clin Cancer Res. 2014 Apr 1;20(7):1747-56 - PubMed
  41. World J Gastroenterol. 2014 Nov 14;20(42):15564-79 - PubMed
  42. Immunity. 2011 Oct 28;35(4):456-66 - PubMed
  43. Cancer. 2010 Apr 1;116(7):1767-75 - PubMed
  44. Int J Radiat Oncol Biol Phys. 2010 Nov 1;78(3):735-42 - PubMed
  45. N Engl J Med. 2012 Mar 8;366(10 ):925-31 - PubMed
  46. Int J Radiat Oncol Biol Phys. 2011 Nov 15;81(4):1128-35 - PubMed
  47. Drug Discov Today Technol. 2005 Autumn;2(3):295-302 - PubMed
  48. Clin Cancer Res. 2006 Feb 1;12(3 Pt 1):878-87 - PubMed
  49. Immunotherapy. 2015;7(8):847-9 - PubMed
  50. J Exp Med. 2013 Aug 26;210(9):1695-710 - PubMed

Publication Types

Grant support