RT Journal Article
SR Electronic
T1 A hypofractionated radiation regimen avoids the lymphopenia associated with neoadjuvant chemoradiation therapy of borderline resectable and locally advanced pancreatic adenocarcinoma
JF Journal for ImmunoTherapy of Cancer
JO J Immunother Cancer
FD BMJ Publishing Group Ltd
SP 45
DO 10.1186/s40425-016-0149-6
VO 4
IS 1
A1 Crocenzi, Todd
A1 Cottam, Benjamin
A1 Newell, Pippa
A1 Wolf, Ronald F.
A1 Hansen, Paul D.
A1 Hammill, Chet
A1 Solhjem, Matthew C.
A1 To, Yue-Yun
A1 Greathouse, Amy
A1 Tormoen, Garth
A1 Jutric, Zeljka
A1 Young, Kristina
A1 Bahjat, Keith S.
A1 Gough, Michael J.
A1 Crittenden, Marka R.
YR 2016
UL http://jitc.bmj.com/content/4/1/45.abstract
AB 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.