关键词: 局限期小细胞肺癌, 淋巴细胞减少, 放疗, 预后, 生存分析, 队列研究

Abstract:

Background and purpose: Despite Radiation-induced 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 comprised 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, 2, 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, 2, 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.

Key words: Limited-stage small cell lung cancer, Lymphopenia, Radiotherapy, Prognosis, Survival analysis, Cohort study