Gastrointestinal Cancer

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SU_17_2169 - Kinetics and Dosimetric Predictors of Acute Radiation-Induced Lymphopenia in Pancreatic Cancer

Sunday, October 21
1:15 PM - 2:45 PM
Location: Innovation Hub, Exhibit Hall 3

Kinetics and Dosimetric Predictors of Acute Radiation-Induced Lymphopenia in Pancreatic Cancer
S. G. Ellsworth1, T. Mereniuk2, H. Zhang3, S. Grossman4, B. H. O'Neil5, R. F. Hobbs6, S. Shahda7, R. Mohan8, F. M. Kong2, and J. Y. Jin9; 1Indiana University, Indianapolis, IN, 2Indiana University Radiation Oncology, Indianapolis, IN, 3Indiana University/Melvin and Bren Simon Cancer Center, Indianapolis, IN, 4Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, 5Indiana University, Simon Cancer Center, Indianapolis, IN, 6Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 7Indiana University School of Medicine, Indianapolis, IN, 8The University of Texas MD Anderson Cancer Center, Houston, TX, 9Department of Radiation Oncology, Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN

Purpose/Objective(s): Radiation (RT) induced lymphopenia (RIL) is an adverse prognostic factor in pancreatic cancer (PC) and is likely due to the irradiation of lymphocytes in the RT field. The goal of this study was to identify dosimetric predictors for high rates of absolute lymphocyte count (ALC) loss during RT for PC.

Materials/Methods: This was a retrospective study of 49 consecutive PC patients who received definitive 5-FU or gemcitabine-based chemoradiation. Median RT dose was 54 Gy (range 50.4-57.5 Gy); 33/49 (67.3%) received gemcitabine, and 16/49 (32.7%) received 5-FU. ALC was plotted against fraction number, and ALC loss kinetics were described based on the following equation: ALC(x) = a + b*(ecx), where ALC(x) represents ALC after x fractions, a represents residual/repopulating lymphocytes, b corresponds to baseline ALC, and the percent per-fraction loss in ALC (PFLAC) is expressed as 100*(1 – ec). Linear regression was used to correlate PFLAC with dosimetric parameters for mean dose to gut, liver, kidney, spleen, cisterna chyli, and estimated dose to immune cells (EDIC), which calculates dose to immune cells according to the % of body lymphocytes contained in each organ. Means were compared with independent samples t-test. Results: Median patient age was 64 years (range 36 to 83), and 32.7% of patients were women. Baseline ALC was normal in 83% of patients, but all patients demonstrated exponential loss in ALC during RT. Mean PFLAC was 9.2% (range 1.8 - 19.5%). PFLAC was moderately correlated with EDIC in the entire cohort of patients (r = 0.58); in the 25 patients with a higher residual/repopulation coefficient (high a), PFLAC was strongly correlated with EDIC (r = 0.85), whereas in patients with a lower residual/repopulation coefficient (low a), PFLAC was not well correlated with EDIC (r = -0.024). Receipt of gemcitabine chemotherapy vs 5FU was correlated with lower a value (mean 74 vs 133, p = 0.01). Multivariate analysis showed that EDIC was a stronger predictor of PFLAC than any individual organ dose in the high-a cohort. Furthermore, the risk of severe (grade 3-4) RIL was strongly correlated with EDIC as well as with PFLAC and other patient-specific parameters describing the kinetics of acute RIL. Conclusion: The kinetics of acute radiation-induced lymphopenia can be calculated on a patient-specific basis, as can dose to the immune organ at risk (EDIC). The rate of ALC loss during RT is closely correlated with EDIC, and both EDIC and the ALC loss rate during treatment are strongly correlated with the risk of severe acute radiation-induced lymphopenia. This work will form the basis for approaches to deliver immune-sparing RT in patients with PC and other malignancies.
Table 1. Predictors of Grade 3-4 lymphopenia.
Characteristic Grade 1-2 (N = 12) Grade 3-4 (N = 37) P (t-test)
Mean age (yrs) 59.4 63.4 0.23
Mean PTV (cc) 371 592 0.006
Mean baseline ALC 2167 1283 <0.001
Mean PFLAC 6.42% 10.3% 0.002
Mean a value 134 80 0.026
Mean EDIC 11.6 15.1 0.003
Mean b value 2031 1172 <0.001

Author Disclosure: S.G. Ellsworth: None. T. Mereniuk: None. H. Zhang: None. R.F. Hobbs: None. S. Shahda: None. R. Mohan: Research Grant; National Cancer Institute. Stock; General Electric. Member, International Advisory Committee; CERN. Member; Scientific Advisory Board. F.(. Kong: Research Grant; Varian, NCI/NIH. Founding President and Board of Director; Sino-American Network for Therapeutic Radiation On. President 2015; American Association of Women Radiologists (AAWR). President 2012-2013; Association for Chinese Professors. Founding Board Member; Sino-American Network for Therapeutic Radiology. J. Jin: Employee; Indiana University Health. Research Grant; Varian medical system, Xstrahl Inc. Honoraria; Varian medical system. Board memebr; SANTRO.

Susannah Ellsworth, MD

Indiana University Radiation Oncology

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