Impacts of post-radiotherapy lymphocyte count on progression-free and overall survival in patients with stage III lung cancer

Abstract

Background: We evaluated the impact of thoracic radiation in patients with non-small cell lung cancer (NSCLC), considering the depletion of total lymphocytes, use or not of chemotherapy, and radiation doses in healthy lung tissue.

Methods: Patients with stage III NSCLC, ECOG 0 to 2, receiving radiotherapy with or without chemotherapy were prospectively evaluated. All patients should be treated with three-dimensional radiotherapy and received biologically effective doses (BED10α/β 10) of 48 to 80 Gy. Peripheral blood lymphocyte total counts were measured at the start of radiotherapy and at 2, 6 and 12 months after radiotherapy. Along with lymphocytes, PTV and doses of 5 Gy and 20 Gy in healthy lung tissue were also evaluated as potential factors influencing overall survival (OS) and progression-free survival (PFS).

Results: A total of 46 patients were prospectively evaluated from April 2016 to August 2019, with a median follow-up of 13 months (interquartile range, 1-39 months). The median of OS of all cohort was 22,8 months (IC 95% 17,6-28,1) and the median PFS was 19,5 months (IC 95%: 14,7-24,2). Most patients received concurrent or neoadjuvant chemotherapy (43; 93.4%). No patient received adjuvant immunotherapy. The lower the lymphocyte loss at 6 months after radiotherapy (every 100 lymphocytes/mcL), the greater the chance of PFS (HR, 0.44; 95%CI, 0.25-0.77; P = 0.004) and OS (HR, 0.83; 95%CI, 0.70-0.98; P = 0.025; P = 0.025). BED was a protective factor for both PFS (HR, 0.52; 95%CI 0.33-0.83; P = 0.0006) and OS (HR, 0.73; 95%CI 0.54-0.97; P = 0.029).

Conclusions: Our results suggest that lymphocyte depletion after radiotherapy reduces tumor control and survival in patients with stage III lung cancer. Radiation doses equal or higher than 60 Gy (BED₁₀ 72 Gy) improve PFS and OS, but they negatively affect lymphocyte counts for months, which reduces survival and the potential of immunotherapy.

Key points: SIGNIFICANT FINDINGS OF THE STUDY: Thoracic irradiation for locally advanced lung cancer depletes T lymphocytes for months. Patients whose lymphocyte loss is lower have better overall survival and progression-free survival.

What this study adds: It is necessary to protect the lymphocyte population, as well as other organs at risk. New forms of irradiation for large fields are needed. Furthermore, could immunotherapy before chemo-radiotherapy, with a greater number of lymphocytes, bring an even better result?

Keywords: Lymphocyte count; non-small cell lung cancer; progression-free survival; survival; thoracic irradiation.

Figure 1

Total lymphocytes versus post‐irradiation time. Data presented as mean ± standard error (mean and 95% confidence interval).

Figure 2

Pearson's correlation between biologic dose and total lymphocytes. r = − 0.732; P = 0.007.