Impact of radiation-induced lymphopenia on prognosis in patients with limited-stage small cell lung cancer: a cohort study

Yihua WANG; Yaqi LI; Yulei PEI; Kailiang WU; Xingwen FAN

doi:10.19401/j.cnki.1007-3639.2025.09.007

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Impact of radiation-induced lymphopenia on prognosis in patients with limited-stage small cell lung cancer: a cohort study

Article | 更新时间：2025-12-31

- Impact of radiation-induced lymphopenia on prognosis in patients with limited-stage small cell lung cancer: a cohort study
- China Oncology Vol. 35, Issue 9, Pages: 867-873(2025)
- 作者机构：
  
  1. 复旦大学附属肿瘤医院胸部放疗科，复旦大学上海医学院肿瘤学系，上海 200032
  2. 太原市中心医院/山西医科大学第九临床医学院肿瘤科，山西太原 030009
- 作者简介：
- 基金信息：
- DOI：10.19401/j.cnki.1007-3639.2025.09.007
  CLC： R734.2
- Received：08 July 2025，
  
  Revised：2025-08-27，
  
  Published：30 September 2025
- 稿件说明：
移动端阅览
Yihua WANG, Yaqi LI, Yulei PEI, et al. Impact of radiation-induced lymphopenia on prognosis in patients with limited-stage small cell lung cancer: a cohort study[J]. China Oncology, 2025, 35(9): 867-873.
DOI：

Yihua WANG, Yaqi LI, Yulei PEI, et al. Impact of radiation-induced lymphopenia on prognosis in patients with limited-stage small cell lung cancer: a cohort study[J]. China Oncology, 2025, 35(9): 867-873. DOI： 10.19401/j.cnki.1007-3639.2025.09.007.

摘要

背景与目的：

尽管放射性淋巴细胞减少与某些恶性肿瘤的不良生存结局相关，但是关于小细胞肺癌（small cell lung cancer，SCLC）的研究证据仍较少。本研究旨在探讨放疗前后淋巴细胞计数是否能预测局限期SCLC（limited-stage SCLC，LS-SCLC）患者的临床预后。

方法：

本研究为一项单中心回顾性队列研究。回顾性分析2007年1月—2017年12月在复旦大学附属肿瘤医院接受根治性放化疗的LS-SCLC患者。纳入标准包括：⑴ 经病理学检查确认为SCLC；⑵ 通过正电子发射计算机体层成像（positron emission tomography and computed tomography，PET/CT）、脑增强磁共振成像（magnetic resonance imaging，MRI）诊断为局限期[美国癌症联合会（American Joint Committee on Cancer，AJCC）第8版TNM分期M0

]

；⑶ 接受了根治性放化疗；⑷ 具有放疗前、放疗期间及放疗后1个月的血常规数据；⑸ 可获得完整的生存、复发及末次随访信息。排除标准包括：⑴ 基线远处转移（AJCC第8版TNM分期M1，包括任何远处淋巴结、器官或骨髓转移）；⑵ 放疗剂量小于50 Gy[以等效生物剂量2 Gy/次计算，即生物有效剂量（biological effective dose，BED）

40 Gy

]

；⑶ 放疗前、放疗期间及放疗后的数据不完整；⑷ 无法获知生存、复发状态或末次随访记录不完整。本研究获得复旦大学附属肿瘤医院伦理委员会的批准（伦理编号：2303271-15），并豁免了患者的知情同意。采集的临床数据包括患者年龄、性别、美国东部肿瘤协作组体能状态（Eastern Cooperative Oncology Group performance status，ECOG PS）评分、吸烟史、肿瘤TNM分期、化疗方案与周期、放疗剂量与分割方式、是否同步放化疗、是否接受预防性颅脑照射（prophylactic cranial irradiation，PCI）；实验室检查数据包括LS-SCLC患者在放疗前、放疗期间及放疗后1个月的淋巴细胞计数，根据不良事件通用术语标准（Common Terminology Criteria for Adverse Events，CTCAE）4.0版对淋巴细胞减少进行分级。使用Kaplan-Meier方法估计无进展生存期（progression-free survival，PFS）和总生存期（overall survival，OS），并用log-rank检验进行比较。

结果：

共纳入170例患者。患者的中位年龄为57岁，男性占77.6%。中位放疗剂量为60 Gy（范围：45~66 Gy)。整组人群的中位PFS为22.0个月，5年PFS率为31.3%，10年PFS率19.8%；中位OS为38.0个月，5年OS率为37.5%，10年OS率24.2%。放疗前，有14例（8.2%）患者出现1~2级淋巴细胞减少；在放疗期间，出现1、2、3、4级淋巴细胞减少的患者分别为7例（4.1%）、22例（12.9%）、111例（65.3%）、24例（14.1%）；在放疗后1个月，1级、2级、3级、4级淋巴细胞减少的患者分别有36例（21.2%）、36例（21.2%）、11例（6.5%）、1例（0.6%）。无论放疗前、中、后，各级淋巴细胞减少患者之间的PFS和OS均无显著差异。

结论：

在免疫治疗前，放疗引起的淋巴细胞减少似乎不影响LS-SCLC患者的预后。

Abstract

Background and purpose:

Despite Radiation-indu

ced lymphopenia has been associated with poor survival outcomes in certain solid tumors

there is limited evidence for small cell lung cancer (SCLC). The purpose of this study was to investigate whether the absolute lymphocyte count before and after radiotherapy could predict the clinical outcomes for limited-stage SCLC (LS-SCLC) patients.

Methods:

This was a single-center

retrospective cohort study. A retrospective analysis of patients evaluated at Fudan University Shanghai Cancer Center from January 2007 to December 2017 was conducted. Inclusion criteria: ⑴ pathologically confirmed small-cell lung cancer; ⑵ limited-stage disease defined by positron emission tomography and computed tomography (PET/CT) and contrast-enhanced brain magnetic resonance imaging (MRI) [American Joint Committee on Cancer (AJCC) 8th edition TNM stage M0

]

; ⑶ receipt of definitive chemoradiotherapy; ⑷ availability of complete blood counts before

during and within 1 month after radiotherapy; ⑸ complete survival

relapse

and last-follow-up information retrievable. Exclusion criteria: ⑴ distant metastasis at baseline (AJCC 8th edition TNM stage M1

including any distant nodal

visceral

or bone-marrow involvement); ⑵ total radiotherapy dose

50 Gy [calculated as an equivalent biological dose at 2 Gy/fraction

i.e.

a biological effective dose (BED)

40 Gy

]

; ⑶ incomplete laboratory data at any scheduled time point; ⑷ inability to ascertain survival or relapse status or insufficient follow-up records. The study protocol was approved by the ethics committee of Fudan University Shanghai Cancer Center (approval number: 2303271-15)

and the requirement for informed consent was waived. Clinical data extracted comprised age

sex

Eastern Cooperative Oncology Group performance status (ECOG PS) score

smoking history

TNM stage

chemotherapy regimen and number of cycles

radiotherapy dose and fractionation schedule

use of concurrent chemoradiotherapy and administration of prophylactic cranial irradiation (PCI). Laboratory data comp

rised serial absolute lymphocyte counts obtained within 1 month before

during and after radiotherapy; lymphopenia was graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared with the log-rank test.

Results:

A total of 170 patients were included. The median age of the patients was 57 years

with 77.6% being male. The median radiation therapy dose was 60 Gy (range: 45-66 Gy). For the entire cohort

the median PFS was 22.0 months

the 5-year PFS rate was 31.3%

and the 10-year PFS rate was 19.8%. The median OS was 38.0 months

the 5-year OS rate was 37.5%

and the 10-year OS rate was 24.2%. Before radiation therapy

14 patients (8.2%) had grade 1-2 lymphocytopenia. During radiation therapy

the number of patients with grade 1

3 and 4 lymphocytopenia was 7 (4.1%)

22 (12.9%)

111 (65.3%)

and 24 (14.1%)

respectively. One month after radiation therapy

the number of patients with grade 1

3 and 4 lymphocytopenia was 36 (21.2%)

36 (21.2%)

11 (6.5%) and 1 (0.6%)

respectively. There were no significant differences in PFS and OS among patients with different grades of lymphocytopenia before

during

or after radiation therapy.

Conclusion:

Before immunotherapy

radiotherapy-induced lymphopenia did not appear to affect the prognosis of patients with LS-SCLC.

关键词

Keywords

references

KIM S Y , PARK H S , CHIANG A C . Small cell lung cancer: a review [J ] . JAMA , 2025 , 333 ( 21 ): 1906.

CHENG Y , SPIGEL D R , CHO B C , et al. Durvalumab after chemoradiotherapy in limited-stage small-cell lung cancer [J ] . N Engl J Med , 2024 , 391 ( 14 ): 1313 - 1327 .

RAMELLA S , IPPOLITO E , D’ANGELILLO R M . Durvalumab in small-cell lung cancer [J ] . N Engl J Med , 2024 , 391 ( 24 ): 2385.

CHO O , OH Y T , CHUN M , et al. Radiation-related lymphopenia as a new prognostic factor in limited-stage small cell lung cancer [J ] . Tumour Biol , 2016 , 37 ( 1 ): 971 - 978 .

SUZUKI R , WEI X , ALLEN P K , et al. Prognostic significance of total lymphocyte count, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio in limited-stage small-cell lung cancer [J ] . Clin Lung Cancer , 2019 , 20 ( 2 ): 117 - 123 . DOI: S1525-7304(18)30309-7 http://doi.org/S1525-7304(18)30309-7

LI H , YU H , LAN S W , et al. Aberrant alteration of circulating lymphocyte subsets in small cell lung cancer patients treated with radiotherapy [J ] . Technol Cancer Res Treat , 2021 , 20 : 15330338211039948.

LIN Y J , KANG Y M , WU Y H , et al. Lymphocytopenia and survival after whole-brain radiotherapy in patients with small-cell lung cancer [J ] . Thorac Cancer , 2023 , 14 ( 14 ): 1268 - 1275 .

KUO P W , BRATMAN S V , SHULTZ D B , et al. Galectin-1 mediates radiation-related lymphopenia and attenuates NSCLC radiation response [J ] . Clin Cancer Res , 2014 , 20 ( 21 ): 5558 - 5569 . DOI: 10.1158/1078-0432.CCR-14-1138 http://doi.org/10.1158/1078-0432.CCR-14-1138

CHEN F , MA L Y , WANG Q , et al. Chemotherapy is a risk factor of lymphopenia before adjuvant radiotherapy in breast cancer [J ] . Cancer Rep , 2022 , 5 ( 7 ): e1525.

SHIRAISHI Y , FANG P , XU C , et al. Severe lymphopenia during neoadjuvant chemoradiation for esophageal cancer: a propensity matched analysis of the relative risk of proton versus photon-based radiation therapy [J ] . Radiother Oncol , 2018 , 128 ( 1 ): 154 - 160 . DOI: S0167-8140(17)32751-2 http://doi.org/S0167-8140(17)32751-2

JING W , LIU Y F , ZHU H , et al. Prognosis of severe lymphopenia after postoperative radiotherapy in non-small cell lung cancer: results of a long-term follow up study [J ] . Clin Transl Radiat Oncol , 2021 , 28 : 54 - 61 . DOI: 10.1016/j.ctro.2021.02.011 http://doi.org/10.1016/j.ctro.2021.02.011

TANG C , LIAO Z X , GOMEZ D , et al. Lymphopenia association with gross tumor volume and lung V5 and its effects on non-small cell lung cancer patient outcomes [J ] . Int J Radiat Oncol Biol Phys , 2014 , 89 ( 5 ): 1084 - 1091 .

DAI D J , TIAN Q Y , SHUI Y J , et al. The impact of radiation induced lymphopenia in the prognosis of head and neck cancer: a systematic review and meta-analysis [J ] . Radiother Oncol , 2022 , 168 : 28 - 36 . DOI: 10.1016/j.radonc.2022.01.003 http://doi.org/10.1016/j.radonc.2022.01.003

MICKEL T A , MOON D H , AVKSHTOL V , et al. Relationship between elective neck irradiation and severe lymphopenia in patients treated with head and neck chemoradiotherapy [J ] . Clin Oncol , 2025 , 44 : 103873 .

DU X Y , WEN S D , SHI R , et al. Peripheral blood lymphocytes differentiation patterns in responses/outcomes to immune checkpoint blockade therapies in non-small cell lung cancer: a retrospective study [J ] . BMC Cancer , 2023 , 23 ( 1 ): 83.

WU S P , LIAO R Q , TU H Y , et al. Stromal PD-L1-positive regulatory T cells and PD-1-positive CD8-positive T cells define the response of different subsets of non-small cell lung cancer to PD-1/PD-L1 blockade immunotherapy [J ] . J Thorac Oncol , 2018 , 13 ( 4 ): 521 - 532 .

YU T , LOK B H . Strategies to target chemoradiotherapy resistance in small cell lung cancer [J ] . Cancers , 2024 , 16 ( 20 ): 3438.

LIU J P , CAO Y , SHAO T Y , et al. Exploring the prognostic impact of differences in treatment strategies for SCLC with different histologies and prognostic factors for C-SCLC: a SEER population-based study [J ] . Heliyon , 2024 , 10 ( 12 ): e32907.

ROSKOSKI R JR . Targeted and cytotoxic inhibitors used in the treatment of lung cancers [J ] . Pharmacol Res , 2024 , 209 : 107465 .

TAUNK N K , RIMNER A , CULLIGAN M , et al. Immunotherapy and radiation therapy for operable early stage and locally advanced non-small cell lung cancer [J ] . Transl Lung Cancer Res , 2017 , 6 ( 2 ): 178 - 185 .

FRĄK M , KRAWCZYK P , KALINKA E , et al. Molecular and clinical premises for the combination therapy consisting of radiochemotherapy and immunotherapy in non-small cell lung cancer patients [J ] . Cancers , 2021 , 13 ( 6 ): 1222.

CHAFT J E , RIMNER A , WEDER W , et al. Evolution of systemic therapy for stages Ⅰ-Ⅲ non-metastatic non-small-cell lung cancer [J ] . Nat Rev Clin Oncol , 2021 , 18 ( 9 ): 547 - 557 .

ROTHSCHILD S I , ZIPPELIUS A , EBOULET E I , et al. SAKK 16/14: durvalumab in addition to neoadjuvant chemotherapy in patients with stage ⅢA(N2) non-small-cell lung cancer-a multicenter single-arm phase Ⅱ trial [J ] . J Clin Oncol , 2021 , 39 ( 26 ): 2872 - 2880 .

MAMOUNAS E P , BANDOS H , WHITE J R , et al. Omitting regional nodal irradiation after response to neoadjuvant chemotherapy [J ] . N Engl J Med , 2025 , 392 ( 21 ): 2113 - 2124 .

HAFFTY B G , MCCALL L M , BALLMAN K V , et al. Impact of radiation on locoregional control in women with node-positive breast cancer treated with neoadjuvant chemotherapy and axillary lymph node dissection: results from ACOSOG Z1071 clinical trial [J ] . Int J Radiat Oncol Biol Phys , 2019 , 105 ( 1 ): 174 - 182 .

TANG J , PAN W Y , ZHAO T , et al. Clinical factors influencing the radiation dose of circulating immune cells during radiotherapy for small cell lung cancer [J ] . J Vis Exp , 2024 ( 210 ): e67243.

ABRAVAN A , EIDE H A , HELLAND Å , et al. Radiotherapy-related lymphopenia in patients with advanced non-small cell lung cancer receiving palliative radiotherapy [J ] . Clin Transl Radiat Oncol , 2020 , 22 : 15 - 21 . DOI: 10.1016/j.ctro.2020.02.005 http://doi.org/10.1016/j.ctro.2020.02.005

WANG X , LU J , TENG F F , et al. Lymphopenia association with accelerated hyperfractionation and its effects on limited-stage small cell lung cancer patients' clinical outcomes [J ] . Ann Transl Med , 2019 , 7 ( 16 ): 385.

ZHANG B Z , LI Y , XU L M , et al. The relationship between the radiation dose of pelvic-bone marrow and lymphocytic toxicity in concurrent chemoradiotherapy for cervical cancer [J ] . Radiat Oncol , 2023 , 18 ( 1 ): 12.

BULLENKAMP J , MENGONI V , KAUR S , et al. Interleukin-7 and interleukin-15 drive CD4 + CD28 null T lymphocyte expansion and function in patients with acute coronary syndrome [J ] . Cardiovasc Res , 2021 , 117 ( 8 ): 1935 - 1948 .

ROMEE R , ROSARIO M , BERRIEN-ELLIOTT M M , et al. Cytokine-induced memory-like natural killer cells exhibit enhanced responses against myeloid leukemia [J ] . Sci Transl Med , 2016 , 8 ( 357 ): 357ra123.

CONLON K C , LUGLI E , WELLES H C , et al. Redistribution, hyperproliferation, activation of natural killer cells and CD8 T cells, and cytokine production during first-in-human clinical trial of recombinant human interleukin-15 in patients with cancer [J ] . J Clin Oncol , 2015 , 33 ( 1 ): 74 - 82 . DOI: 10.1200/JCO.2014.57.3329 http://doi.org/10.1200/JCO.2014.57.3329

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