Lymphopenia predicts response to stereotactic radiosurgery in lung cancer patients with brain metastases

  • Yuping D. Li
  • Jason B. Lamano
  • Gurvinder Kaur
  • Jonathan B. Lamano
  • Dorina Veliceasa
  • Dauren Biyashev
  • Timothy Kruser
  • Orin BlochEmail author
Clinical Study



Stereotactic radiosurgery (SRS) can enhance immune activation and improve disease control through stimulation of anti-tumor immunity. However, patients with cancer receiving chemotherapy are often immunosuppressed, which may impact the efficacy of SRS. Here we investigate the relationship between systemic lymphopenia and response to SRS in patients with brain-metastatic lung cancer.


We reviewed 125 patients with lung cancer brain metastases treated with SRS between January 2014 and May 2017. Complete blood counts from the time of SRS were reviewed, and lymphopenia was defined as absolute lymphocyte count < 1×109 cells/L. Kaplan–Meier survival analysis and cox proportional-hazards models were used to evaluate risks of progression and death.


The median age was 65 years (range 43–86), with 54% female patients. Lymphopenia was present in 60 patients. In univariate analysis, lymphopenic patients had significantly shorter PFS (HR = 2.995, p < 0.0001) and OS (HR = 3.928, p < 0.0001). When accounting for age, gender, smoking history, ECOG score, surgery, and tumor histology in a multivariate model, lymphopenia remained significantly predictive of worse PFS (HR = 1.912, p = 0.002) and OS (HR = 2.257, p < 0.001). Patients who received immunotherapy within 3 months of SRS demonstrated significantly shorter PFS (HR = 3.578, p = 0.006) and OS (HR = 6.409, p = 0.001) if lymphopenic.


Brain-metastatic lung cancer patients with lymphopenia treated with SRS had significantly worse PFS and OS. The effect of lymphopenia was even more pronounced in patients receiving immunotherapy. These data demonstrate the significant impact of deficient immunity on disease control and survival. Lymphopenic patients may benefit from interventions to improve immune function prior to SRS for brain metastases.


Lymphopenia Stereotactic radiosurgery Radiation Brain metastasis Immunosuppression Lung cancer 



This work was supported by the Howard Hughes Medical Institute Medical Student Research Fellows program (YL) as well as by the National Institutes of Health (NIH)/National Cancer Institute (NCI) Ruth L. Kirschtein National Research Service Award F30 (CA206413; JBL), NIH/NCI R01 (CA164714; OB), and NIH/National Institute of Neurological Disorders and Stroke (NINDS) R00 (NS078055; OB). GK was supported by NIH/NINDS F32 (NS101884).

Compliance with ethical standards

Conflict of interest

The authors report no conflicts of interest.

Supplementary material

11060_2019_3169_MOESM1_ESM.docx (26 kb)
Supplementary material 1 (DOCX 26 kb)


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Neurological Surgery, Feinberg School of MedicineNorthwestern UniversityChicagoUSA
  2. 2.Stritch School of MedicineLoyola University ChicagoMaywoodUSA
  3. 3.Department of Radiation Oncology, Feinberg School of MedicineNorthwestern UniversityChicagoUSA
  4. 4.Department of Neurological SurgeryUniversity of California – DavisSacramentoUSA

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