Radiation induced lymphopenia (RIL) is a common radiation-related toxicity that has been recognized for over a century but often ignored as clinically inconsequential. However, accumulating evidence has demonstrated strong association of high grade RIL (seen in 30-50% of patients) with poor prognosis. The pervasive role of radiotherapy in the curative management of solid tumors supports the need to develop mitigating strategies, particularly for patients with a high risk of developing grade 4 (G4) RIL. We have compelling evidence from both clinical and preclinical work that severe RIL impacts cancer control and therapy effectiveness, and methods to reduce RIL may improve treatment outcomes. To further develop these approaches for clinical translation, we have proposed 2 specific aims.
In aim 1, we will build on our initial prediction model for G4 RIL and leverage our large database of esophageal cancer patients who have completed chemoradiation (CRT) to develop a better predictive model for G4 RIL so that we can rapidly and efficiently identify the highest risk patients for mitigating strategies.
In aim 2, we will determine the feasibility and safety of raising the baseline lymphocyte levels by autologous lymphocyte infusion (ALI) prior to initiating CRT. Fundamentally, this research will allow us to develop the necessary computational tool capable of properly identifying patients at risk for developing severe RIL, and complete a small feasibility and safety study of using ALI as a way to raise the baseline pre-treatment lymphocyte levels so that the probability of developing G4 RIL could be possibly curtailed. By targeting the at-risk patients to receive RIL mitigating strategies, we will hopefully be able to improve the cancer outcomes of standard cancer therapies, and build on current innovative strategies of immunotherapy and radiation combinations.

Public Health Relevance

Radiation therapy, a key pillar in the management of cancers, causes a common yet ignored side effect of radiation induced lymphopenia (RIL). Severe RIL has been linked to poor outcomes of patients, presumably due to reduced immune surveillance thereby increasing disease recurrence after radiation therapy. We propose developing a prediction model to help identify who are most at risk for developing severe RIL, and conduct a pilot study to help reduce the impact of RIL so that clinical outcomes for these at-risk patients will improve in the future.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21CA240881-01
Application #
9807793
Study Section
Special Emphasis Panel (ZCA1)
Program Officer
Vikram, Bhadrasain
Project Start
2019-09-13
Project End
2021-08-31
Budget Start
2019-09-13
Budget End
2020-08-31
Support Year
1
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Texas MD Anderson Cancer Center
Department
Radiation-Diagnostic/Oncology
Type
Hospitals
DUNS #
800772139
City
Houston
State
TX
Country
United States
Zip Code
77030