Treatment-duration is related to changes in peripheral lymphocyte counts during definitive radiotherapy for unresectable stage III NSCLC

Abstract

Background To investigate the potential impact of fractionation regimes and overall treatment time (OTT) on lymphopenia during definitive radiotherapy (RT) and its associations with patient outcomes in non-small cell lung cancer (NSCLC). Methods Subjects consisted of 115 patients who had received definitive chemoradiation therapy (CRT) with different doses and fractions for unresectable stage III NSCLC. Clinical and laboratory records were reviewed to assess the changes in total lymphocyte counts (TLCs) during definitive RT. The associations of the TLCs with the clinical and treatment features, and outcomes were analyzed. Results The median reduction of TLCs in the entire cohort was 1300 cells/μL (interquartile range [IQR], 950–1510 cells/μL). Of all patients, 63 (54.8%) experienced severe lymphopenia (SL) (TLC nadir < 500 cells/μL), which occurred at a median of the 5th week following RT initiation, not at the completion of RT or upon treatment with maximal doses. SL risk was increased over the first 5 weeks (odds ratio [OR] = 3.455, P = 0.007), after which, no increased risk was observed (OR = 0.562, P = 0.216). The median TLCs remained low and failed to recover to the initial normal values of their pre-RT level after 2 months of RT completion. Patients without SL exhibited significantly improved progression-free survival (hazard ratio [HR] = 0.544, P = 0.010) and overall survival (HR = 0.463, P = 0.011) after controlling for confounding variables in multivariate analyses. The incidence of SL was significantly lower (71.1% reduction in risk (OR = 0.289, P = 0.007)) in patients who received hypofractionated RT with an OTT within 4 weeks, compared to those who had an OTT of more than 4 weeks (32.1% vs 62.1%, P = 0.006). Multivariate analyses revealed that OTT within 4 weeks (OR = 0.322, P = 0.032) was significantly associated with a decreased risk of developing SL after controlling for confounding factors. Conclusions Hypofractionated RT was significantly associated with a decreased risk of SL and improved survival during definitive radiotherapy for unresectable stage III NSCLC. Electronic supplementary material The online version of this article (10.1186/s13014-019-1287-z) contains supplementary material, which is available to authorized users.

Association Between Circulating Lymphocyte Populations and Outcome After Stereotactic Body Radiation Therapy in Patients With Hepatocellular Carcinoma

“…Nowadays, the recognition that the immune system plays a vital role in tumor surveillance and the advent of immunotherapy has renewed the focus on preserving a pool of functioning lymphocytes in circulation. RT-induced lymphopenia (RIL) has been associated with poor outcome in liver cancer (11, 15), breast cancer (16), glioblastoma (17), nasopharyngeal cancer (18), non-small cell lung cancer (NSLC) (19), pancreatic cancer (20), and other tumors (21–23). Nevertheless, few reports have focused on the impact of SBRT on the values of different CLP types, including CD3 + T, CD19 + B, and CD15 + 56 + NK cells and the prognostic values of CLPs for survival in HCC patients.…”

Prognosis of severe lymphopenia after postoperative radiotherapy in non-small cell lung cancer: Results of a long-term follow up study

“…Prolonged RT duration may contribute to severe lymphopenia. Grade 3 to 4 lymphopenia occurred in 54.8% of patients at a median of the 5th week after RT started [20] . Patients with treatment duration >4 weeks had a 28.9% increase in the risk of grade 3–4 lymphopenia, compared to those with the treatment duration of 4 weeks or less (32.1% vs. 62.1%, p = 0.006).…”

“…This is not the same as the lymphopenia caused by radiotherapy. Several studies have indicated that lymphocyte counts decline exponentially during radiation, reaching nadir between 3 and 5 weeks from the start of radiotherapy [20] , [24] . In addition, the lymphocyte counts are not restored fully for nearly half of the patients even 1–2 months after completing radiation therapy [26] .…”

Radiotherapy in the Era of Immunotherapy With a Focus on Non-Small-Cell Lung Cancer: Time to Revisit Ancient Dogmas?

“…Therefore, the optimization of dose-fractionation chemoradiotherapy regimens for locally advanced disease in the context of IO combination requires careful consideration, as conventional fractionated regimens have been associated with lymphopenia and immune suppression in several types of cancers ( 16 , 17 ). In this perspective, moderately hypofractionated (2.5-4 Gy per fraction) schedules could be of interest because the acceleration of treatment allowed by hypofractionated schedules could reduce the amount of blood passing through the beam and thus the duration and the severity of radiation-induced T-cell suppression and lymphopenia ( 43 , 44 ). Indeed, in their study of 115 patients with unserectable stage III NSCLC treated by definitive RT, Zhao et al found that overall treatment time within 4 weeks was significantly associated with a decreased risk of developing severe lymphopenia in multivariate analysis ( 44 ).…”

“…In this perspective, moderately hypofractionated (2.5-4 Gy per fraction) schedules could be of interest because the acceleration of treatment allowed by hypofractionated schedules could reduce the amount of blood passing through the beam and thus the duration and the severity of radiation-induced T-cell suppression and lymphopenia ( 43 , 44 ). Indeed, in their study of 115 patients with unserectable stage III NSCLC treated by definitive RT, Zhao et al found that overall treatment time within 4 weeks was significantly associated with a decreased risk of developing severe lymphopenia in multivariate analysis ( 44 ). Notably, in this setting of locally advanced disease, the question whether the addition of IO to (chemo-)radiotherapy can act as a radiosensitizer through a synergistic effect remains open for two main reasons.…”