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Meta-Analysis
. 2015 Oct;13(10):1225-31.
doi: 10.6004/jnccn.2015.0151.

Survival in Patients With Severe Lymphopenia Following Treatment With Radiation and Chemotherapy for Newly Diagnosed Solid Tumors

Stuart A Grossman  1 , Susannah Ellsworth  1 , Jian Campian  1 , Aaron T Wild  1 , Joseph M Herman  1 , Dan Laheru  1 , Malcolm Brock  1 , Ani Balmanoukian  1 , Xiaobu Ye  1
Affiliations
Meta-Analysis

Survival in Patients With Severe Lymphopenia Following Treatment With Radiation and Chemotherapy for Newly Diagnosed Solid Tumors

Stuart A Grossman et al. J Natl Compr Canc Netw. 2015 Oct.

Abstract

Background: The immune system plays an important role in cancer surveillance and therapy. Chemoradiation can cause severe treatment-related lymphopenia (TRL) (<500 cells/mm3) that is associated with reduced survival.

Materials and methods: Data from 4 independent solid tumor studies on serial lymphocyte counts, prognostic factors, treatment, and survival were collected and analyzed. The data set included 297 patients with newly diagnosed malignant glioma (N=96), resected pancreatic cancer (N=53), unresectable pancreatic cancer (N=101), and non-small cell lung cancer (N=47).

Results: Pretreatment lymphocyte counts were normal in 83% of the patient population, and no patient had severe baseline lymphopenia. Two months after initiating chemoradiation, 43% developed severe and persistent lymphopenia (P=.001). An increased risk for death was attributable to TRL in each cancer cohort (gliomas: hazard rate [HR], 1.8; 95% CI, 1.13-2.87; resected pancreas: HR, 2.2; 95% CI, 1.17-4.12; unresected pancreas: HR, 2.9; 95% CI, 1.53-5.42; and lung: HR, 1.7; 95% CI, 0.8-3.61) and in the entire study population regardless of pathologic findings (HR, 2.1; 95% CI, 1.54-2.78; P<.0001). Severe TRL was observed in more than 40% of patients 2 months after initiating chemoradiation, regardless of histology or chemotherapy regimen, and was independently associated with shorter survival from tumor progression.

Conclusions: Increased attention and research should be focused on the cause, prevention, and reversal of this unintended consequence of cancer treatment that seems to be related to survival in patients with solid tumors.

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Figures

Figure 1
Figure 1
Changes in total lymphocyte count (TLC) over time in each individual disease cohort: (A) high-grade glioma; (B) resected pancreas cancer; (C) unresected pancreas cancer; and (D) non–small cell lung cancer.
Figure 2
Figure 2
Changes in lymphocyte count over time in the entire group of patients. Abbreviation: TLC, total lymphocyte count.
Figure 3
Figure 3
Relationship between survival and grade III/IV treatment-related lymphopenia in 297 patients with solid tumors. Pooled hazard ratio, 2.1; 95% CI, 1.54–2.78; P<.0001. Abbreviations: NSCLC, non–small cell lung cancer; TLC, total lymphocyte count.
Figure 4
Figure 4
Overall survival (stratified by total lymphocyte count) 2 months after initiating radiation therapy.
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