Radiation Biology

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SU_38_2380 - Factors Affecting Kinetics of Acute Radiation-Induced Lymphopenia in Patients with Gastrointestinal Cancer

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

Factors Affecting Kinetics of Acute Radiation-Induced Lymphopenia in Patients with Gastrointestinal Cancer
S. G. Ellsworth1, H. Zhang2, T. Mereniuk3, N. Agrawal2, R. C. Zellars2, F. M. Kong3, and J. Y. Jin2; 1Indiana University, Indianapolis, IN, 2Department of Radiation Oncology, Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN, 3Indiana University Radiation Oncology, Indianapolis, IN

Purpose/Objective(s): Acute radiation (RT)-induced lymphopenia (RIL) is an adverse prognostic factor in pancreatic and rectal cancers. This study aimed to identify patient-specific parameters describing the kinetics of acute RIL and risk factors for high rates of lymphocyte loss during RT.

Materials/Methods: This was a retrospective study of 93 consecutive patients with pancreatic (PC; n=49), rectal (n=36), and anal (n=8) cancer, treated with concurrent chemotherapy (CT)/RT with 5-FU (n=52), gemcitabine (GEM; n=33) or 5FU/mitomycin C (MMC; n=8). Median RT dose was 54 Gy (range 50.4 – 59.4 Gy). Absolute lymphocyte count (ALC) was plotted against fraction number, and a best-fit line for each patient was calculated according to the equation ALCx = a + becx. ALCx represents ALC after x fractions, a is a constant representing residual/repopulating lymphocytes, b corresponds to baseline ALC, and per-fraction loss in ALC (PFLAC) equals 100*(1-ec). Between-group differences were compared using analysis of variance (ANOVA) and paired t-test; linear regression was used to analyze correlations between PFLAC and clinical parameters including age, PTV size, and baseline and end-treat ALC.

Results: Median age was 60 years; 35% were women. 90% had normal baseline ALC and median PFLAC was 10.6% (range 1.8 – 48.3). PFLAC was correlated with end-treat ALC (r=-0.36, p =0.001); PFLAC also differed by treated site (mean 16.1 vs 9.2% in patients undergoing pelvic vs. abdominal radiation, p <0.001) and chemotherapy (mean 10.0, 12.3, and 24.2% in patients receiving GEM, 5FU, and 5FU/MMC, respectively, p < 0.001) and was moderately correlated with PTV volume (r = 0.4, p < 0.001). Mean a was affected by treated site (94.6 vs. 275.7 in abdominal vs. pelvic RT, p < 0.001) and CT (74.7, 219.8, and 242.5 in patients receiving GEM, 5FU, and 5FU/MMC, respectively, p < 0.001). In patients with PC, mean a was 75 in GEM patients and 133 in 5FU patients, suggesting that CT effects on a are independent of treated site. 72 patients (77%) developed grade 3-4 lymphopenia. Risk of severe RIL was not correlated with PTV size (mean PTV 1617 vs 1685 cc in patients with grade 0-2 vs 3-4 RIL, p = 0.85) but was strongly correlated with RIL kinetics, including a (mean 164 vs 254 in patients with vs. without grade 3-4 RIL, p = 0.05), PFLAC (mean 14.0 vs 8.5% in patients with grade 0-2 vs 3-4 RIL, p = 0.003), and baseline ALC (mean 2100 vs 1500 in patients with grade 0-2 vs. 3-4 RIL, p < 0.001).

Conclusion: Acute RIL is characterized by exponential decline in lymphocyte counts that can be mathematically characterized on a patient-specific basis. Patients treated with GEM/RT have lower per-fraction ALC loss rates but lower repopulation, while patients treated with 5-FU/MMC/RT have high loss rates but a relatively higher repopulation capacity. Given the correlation of RIL with inferior outcomes, interventions to reduce the risk and severity of RIL may improve survival in patients with gastrointestinal cancers.

Author Disclosure: S.G. Ellsworth: None. H. Zhang: None. T. Mereniuk: None. N. Agrawal: None. R. Zellars: Board Member; Indiana University Health Physicians. 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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