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Review
. 2022 Jun 20;14(12):3024.
doi: 10.3390/cancers14123024.

Severe Radiation-Induced Lymphopenia Affects the Outcomes of Esophageal Cancer: A Comprehensive Systematic Review and Meta-Analysis

Dongjun Dai  1 , Qiaoying Tian  1 , Genhua Yu  1 , Yongjie Shui  1 , Hao Jiang  2   3 , Qichun Wei  1   2
Affiliations
Review

Severe Radiation-Induced Lymphopenia Affects the Outcomes of Esophageal Cancer: A Comprehensive Systematic Review and Meta-Analysis

Dongjun Dai et al. Cancers (Basel). .

Abstract

The aim of the current study was to evaluate the influence of severe radiation-induced lymphopenia (RIL) on the outcomes of esophageal cancer (EC). A systematic review and meta-analysis was performed through the PRISMA guideline. Seventeen studies were included in the current systematic review, with eight included in the meta-analyses. Meta-analyses found that severe RIL was associated with lower pathologic complete response (pCR) rate (odds ratio (OR) = 0.44, 95% confidence interval (CI) = 0.30-0.66, I2 = 0%), inferior overall survival (OS) (hazard ratio (HR) = 1.50, 95% CI = 1.29-1.75, I2 = 6%), and worse progression-free survival (PFS) (HR = 1.70, 95% CI = 1.39-2.07, I2 = 0%) of EC patients. The lymphocyte nadir was found during 4-6 weeks after the start of radiotherapy. The leading dosimetric factors associated with severe RIL included larger PTV, higher dose to heart and body, and higher effective dose to the immune cells (EDIC). Clinical risk factors for RIL mainly comprised lower baseline ALC, higher tumor length and clinical stage, and distal EC. In conclusion, severe RIL might be associated with a lower pCR rate and worse OS and PFS of EC patients. Minimizing the dosimetric risk factors, especially in patients with clinical risk factors, might benefit their outcomes.

Keywords: effective dose to the immune cells; esophageal cancer; lymphopenia; pathologic complete response; radiation therapy; survival outcomes.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Flowchart of selection process in this systematic review. This is the PRISMA 2020 flow diagram for new systematic reviews, which only includes searches of databases and registers.
Figure 2
Figure 2
Forest plots depicting meta-analyses for the association between severe RIL and the outcomes of EC patients; meta-analyses for the correlation of severe RIL and pCR (a), OS (b), and PFS (c) of EC patients. The big diamond at the bottom of the plot symbolizes the pooled OR or HR of all studies. The diamond’s width corresponds to 95% CI. For these included multivariate analyses, Zhou X et al. included variables of lymphopenia, tumor length, and baseline ALC. Li Q et al. included variables of lymphopenia, pretreatment platelets, chemotherapy, and interval to surgery in the meta-analysis of pCR, and included age, sex, primary tumor length, clinical stage, chemotherapy, interval to surgery, and pCR status in the meta-analysis of PFS. Fang P et al. included variables of lymphopenia, age, current smoker, clinical stage, histology, differentiation, tumor length and location, radiotherapy dose and modality, induction chemotherapy, and chemotherapy regimen. Xu H et al. included variables of lymphopenia, sex, tumor location and length, induction chemotherapy, clinical stage, radiotherapy modality, and baseline albumin and hemoglobin. Liu M et al. included variables of lymphopenia; age; sex; ECOG score; tumor location; clinical stage; chemotherapy; prescribed radiotherapy dose; pretreatment NLR; mean TVB dose; TVB V5, V10, and V20; and EDIC. Wang X et al. included variables of lymphopenia, age, sex, smoking, drinking, tumor length and location, clinical stage, treatments (concurrent chemotherapy and chemotherapy regimen), radiotherapy technology and dose, and baseline ALC. Zhang E et al. included variables of lymphopenia, clinical stage, and surgery. Deng W et al. included variables of lymphopenia, baseline ALC, sex, age, ECOG score, tumor length and location, histology, differentiation, clinical stage, and treatments (induction and concurrent chemotherapy and surgery).
Figure 3
Figure 3
The tendency of ALC in EC patients who received CRT. (a) Serial median ALC in EC patients who received CRT from various studies. (b) Merged mean ALC in EC patients who received CRT; the circle represents the mean median ALC of studies and the error bars represent the standard deviation.
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