The Association Between Chemoradiation-related Lymphopenia and Clinical Outcomes in Patients With Locally Advanced Pancreatic Adenocarcinoma

Abstract

Objectives Lymphopenia is a common consequence of chemoradiation therapy yet is seldom addressed clinically. This study was conducted to determine if patients with locally advanced pancreatic cancer (LAPC) treated with definitive chemoradiation develop significant lymphopenia and if this affects clinical outcomes. Methods A retrospective analysis of patients with LAPC treated with chemoradiation at a single institution from 1997 to 2011 was performed. Total lymphocyte counts (TLCs) were recorded at baseline and then monthly during and after chemoradiation. The correlation between treatment-induced lymphopenia, established prognostic factors, and overall survival was analyzed using univariate Cox regression analysis. Important factors identified by univariate analysis were selected as covariates to construct a multivariate proportional hazards model for survival. Results A total of 101 patients met eligibility criteria. TLCs were normal in 86% before chemoradiation. The mean reduction in TLC per patient was 50.6% (SD, 40.6%) 2 months after starting chemoradiation (P< 0.00001), and 46% had TLC< 500 cells/mm3. Patients with TLC < 500 cells/mm3 2 months after starting chemoradiation had inferior median survival (8.7 vs. 13.3mo, P= 0.03) and PFS (4.9 vs. 9.0mo, P = 0.15). Multivariate analysis revealed TLC< 500 cells/mm3 to be an independent predictor of inferior survival (HR= 2.879, P= 0.001) along with baseline serum albumin (HR= 3.584, P = 0.0002), BUN (HR = 1.060, P= 0.02), platelet count (HR= 1.004, P = 0.005), and radiation planning target volume (HR= 1.003, P= 0.0006). Conclusions Severe treatment-related lymphopenia occurs frequently after chemoradiation for LAPC and is an independent predictor of inferior survival.

Stem Cell Transfusion Restores Immune Function in Radiation-Induced Lymphopenic C57BL/6 Mice

“…RIL is associated with treatment of many tumors (lung, colon, pancreas, breast, sarcomas, and glioblastoma) and associated with poor clinical outcomes (2,3,5,6). The biologic mechanisms leading to RIL are not clearly understood.…”

“…The biologic mechanisms leading to RIL are not clearly understood. T-cell renewal occurs approximately every 60 to 90 days (2,5). If the effect of radiation was only on circulating lymphocytes, and assuming that all circulating T cells were destroyed by irradiation, lymphopenia should not be observed for more than 90 days.…”

“…2). RIL is frequently observed in cancer patients undergoing radiotherapy to various sites, including brain, thorax, abdomen, and pelvis (2)(3)(4)(5). Recent clinical data indicate that RIL was associated with poor clinical outcome in patients with carcinomas of the lung, colon, pancreas, breast, sarcomas, and glioblastoma (2)(3)(4)6).…”

Comparison of proton therapy and intensity modulated photon radiotherapy for locally advanced non-small cell lung cancer: considerations for optimal trial design

“…The increased conformity of proton therapy spares circulating lymphocytes through decreased radiation exposure and fractionation to major blood pools, such as the heart. Other research has shown that lymphopenia and post treatment circulating lymphocyte levels are independent predictors of survival (22,23). These collective findings suggest that proton therapy may improve outcomes through lymphocyte sparing.…”

Tolerance and efficacy of palliative radiotherapy for advanced pancreatic cancer: A retrospective analysis of single-institutional experiences

“…The majority of patients who have pancreatic cancer in their initial evaluation have a combination of factors, such as advanced age, poor performance status, medical comorbidity or tumour-related conditions, such as anorexia; thus, they are poor candidates for aggressive therapy, such as CRT. It is important to perform a stratification of patients into treatment groups on the basis of prognostic factors (16,17).…”