Lymphopenia association with accelerated hyperfractionation and its effects on limited-stage small cell lung cancer patients' clinical outcomes.

Background: An assessment of trends in lung cancer patient survival is very important to determine the outcomes and to modulate where advancements should be made. This study investigated whether the absolute lymphocyte count just after chemoradiation (after-ALC) and 3 months after chemoradiation initiation (post-ALC) could predict limited-stage small cell lung cancer (LS-SCLC) patients' clinical outcomes.

Methods: We retrospectively reviewed 304 patients who were newly diagnosed with LS-SCLC and received treatment with chemoradiation (CRT). Finally we collected data at the time of pretreatment, after-ALC and post-ALC from 226 patients. Kaplan-Meier survival curves and log-rank statistics were used to assess the prognostic significance of after-ALC and post-ALC for survival rates. Cox proportional hazards models were used to generate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results: Two hundred and twenty-six patients had a documented ALC pretreatment, just after CRT and 3 months after CRT. Relative lymphopenia of pre-treatment ALC was in 47.8% of patients, whereas the lymphopenia (<655 cells/mm) proportion was increased to 61.1% just after CRT, and the lymphopenia (<1,430 cells/mm) proportion continued to rise to 70.4% at the time of 3 months after initiating CRT. After-ALC lymphopenia patients showed inferior median OS (18.1 36.0 months, P<0.001) and similar PFS (9.7 26.2 months, P<0.001) compared to patients without lymphopenia. Multivariate analysis demonstrated after-ALC <655 cells/mm and post-ALC <1,430 cells/mm (HR: 1.339; P=0.038) had a 105% and 33% (HR: 2.056; P<0.001) increase in hazards of death respectively. Similarly, after-ALC <655 cells/mm and post-ALC <1,430 cells/mm had a 160% (HR: 2.606; P=0.002) and 40% (HR: 1.409; P=0.015) increase in hazards of progression respectively. Furthermore, hyperfractionated RT showed more likely to cause lymphopenia in patients than conventional fractionated RT.

Conclusions: Nearly half of LS-SCLC patients treatment with CRT experienced severe lymphopenia and more than half patients exhibited prolonged lymphopenia. Statistical significance that lymphopenia after treatment was associated with decreased survival was obviously observed. Further study is warranted, given that explanation lymphopenia is a mechanism for shorter survival or just a predictor.