Radiotherapy-related lymphopenia in patients with advanced non-small cell lung cancer receiving palliative radiotherapy

Azadeh Abravan; Hanne Astrid Eide; Åslaug Helland; Eirik Malinen

doi:10.1016/j.ctro.2020.02.005

Radiotherapy-related lymphopenia in patients with advanced non-small cell lung cancer receiving palliative radiotherapy

Clin Transl Radiat Oncol. 2020 Feb 19:22:15-21. doi: 10.1016/j.ctro.2020.02.005. eCollection 2020 May.

Authors

Azadeh Abravan^{1

2}, Hanne Astrid Eide^{3

4}, Åslaug Helland^{3

4}, Eirik Malinen^{1

2}

Affiliations

¹ Department of Medical Physics, Oslo University Hospital, Oslo, Norway.
² Department of Physics, University of Oslo, Oslo, Norway.
³ Department of Oncology, Oslo University Hospital, Oslo, Norway.
⁴ Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.

Abstract

Background: Lymphopenia during radiotherapy (RT) may have an adverse effect on treatment outcome. The aim of this study is to investigate associations between lymphopenia and RT parameters in patients with advanced lung cancer. Moreover, to investigate the prognostic role of lymphopenia, blood protein levels, and treatment and patient-related factors.

Material and methods: Sixty-two advanced stage non-small cell lung cancer (NSCLC) patients were retrospectively analyzed. Blood counts were available prior to, during, and after RT (3Gyx10). For each patient, a thoracic volume of interest (VOI) -including thoracic soft tissue and trabecular bone- was obtained by applying a CT window of -500 to 1200 HU in the planning CT. Dose parameters from thoracic VOI and other regions including lungs and vertebrae were calculated. Association between risk of lymphopenia ≥ G3 (lymphocytes at nadir according to CTCAE v4.0) and therapeutic parameters was investigated using Logistic regression. Relationships between overall survival (OS) and RT dose parameters, baseline blood counts and protein levels, and clinical factors were evaluated using Log-rank and Cox models.

Result: Mean thoracic RT dose (odds ratio [OR] 1.67; p = 0.04), baseline lymphocytes (OR 0.65; p = 0.01), and corticosteroids use (OR 6.07; p = 0.02) were significantly associated with increased risk of lymphopenia ≥ G3 in multivariable analysis. Worse OS was associated with high mean thoracic RT dose, high CRP/Albumin, large tumor volume and corticosteroids use (p < 0.05, univariate analysis), but not with lymphopenia ≥ G3. CRP/Albumin ratio > 0.12 (hazard ratio [HR] 2.28, p = 0.03) and corticosteroid use (HR 2.52, p = 0.01) were independently associated with worse OS.

Conclusion: High thoracic RT dose gave a higher risk of lymphopenia ≥ G3; hence limiting dose volume to the thorax may be valuable in preventing severe lymphopenia for patients receiving palliative fractionated RT. Still, lymphopenia ≥ G3 was not associated with worse OS. however, high baseline CRP/Albumin was associated with poorer OS and may carry important information as a prognostic factor of OS in advanced NSCLC receiving palliative RT.

Keywords: C-reactive protein/Albumin; CRP, C-Reactive Protein; CRT, Chemo-radiotherapy; CT, Computed Tomography; CTCAE, Common Terminology Criteria for Adverse Events; Corticosteroid; ECOG, Eastern Cooperative Oncology Group; GTV, Gross Tumor Volume; HR, Hazard Ratio; Hematologic toxicity; Lung cancer; Lymphopenia; NSCLC, Non-Small Cell Lung Cancer; OR, Odds Ratio; OS, Overall Survival; Overall survival; RT, Radiotherapy; Radiotherapy; VOI, Volume of Interest.