<p>Pre/Post-Treatment Dynamic of Inflammatory Markers Has Prognostic Value in Patients with Small Hepatocellular Carcinoma Managed by Stereotactic Body Radiation Therapy</p>

Abstract

The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are inflammatory indexes that may reflect immune response to tumors and prognosis. We investigated the prognostic values of pre-treatment and post-treatment NLR and PLR and changes in those ratios in patients with small hepatocellular carcinoma (sHCC) treated with stereotactic body radiation therapy (SBRT). Patients and methods: Sixty patients who received SBRT were retrospectively reviewed. NLR and PLR were calculated by division of neutrophil and platelet counts, respectively, by lymphocyte counts. Independent factors for progression-free survival (PFS) and overall survival (OS) were determined by the Kaplan-Meier method, log-rank test, and Cox multivariate regression. Hazard ratios (HRs) and 95% confidence intervals (CIs) were also calculated. Results: The median follow-up was 36.9 (range: 4.1-73.5) months. Median PFS was 21.4 (range: 1.8-66.9) months. The 1-year and 2-year PFS rates were 76.7% and 55.0%, respectively. The 1-year and 2-year OS rates were 95.0% and 78.3%, respectively. In multivariate analysis, post-treatment PLR ≥263.0 indicated both poor PFS (HR: 3.70; 95% CI: 1.07-12.76, p=0.038) and OS (HR: 3.23; 95% CI: 1.01-9.11, p=0.043) for sHCC patients treated with SBRT. In addition, the presence of hepatitis infection and a low level of red blood cell count were also proved to be significantly associated with patients' poor prognosis (p<0.05 for each). Post-treatment increase in NLR ≥2.7-fold was shown to be a negative independent predictor of inferior OS (HR: 3.43; 95% CI: 1.14-10.38, p=0.029). Conclusion: High post-treatment PLR and change in NLR ≥2.7-fold were associated with poor prognosis in patients treated with SBRT and might be considered as reliable and independent prognostic biomarkers for patients with sHCC.

Dynamic Changes in Neutrophil-to-Lymphocyte Ratio are Associated with Survival and Liver Toxicity Following Stereotactic Body Radiotherapy for Hepatocellular Carcinoma

“…In another study by Zhuang et al, a decrease in circulating blood cells was noted in 50 patients receiving SBRT of 48-60 Gy for small HCC. 24 Although not addressed statistically, the lymphocyte counts had a larger decline (dropping by nearly half the pretreatment value) compared to other cells. We also found that the differential radiation response of immune cells leads to a significantly elevated NLR and PLR post-SBRT.…”

“…SBRT is well known as an extremely precise, highdose form of radiation therapy (RT) targeting a relatively small region encompassing the tumors while avoiding normal tissues from clinically intolerable radiation exposure. However, even with the favourable property of sharp dose fall-off and small field size compared to conventionally fractionated radiotherapy, SBRT still produces a certain degree of systemic effects on peripheral blood components during a course of limited fractionations for patients with lung, 23 pancreas, 18 and liver 12,24 cancers. In vivo and in vitro investigations showed that human peripheral blood cells differ in their radiosensitivity, with lymphoid cells being extremely radiosensitive.…”

“…Only one prior study has evaluated the predictive role of NLR and PLR in a dynamic setting in HCC patients treated with SBRT. 24 They focused on a population with small HCC and CTP class A liver function, among them only 50 patients had an available peritreatment immune profile (taken at median 7 days before and 10 days after SBRT) for analysis. They found that the low post-SBRT PLR <263 and limited NLR kinetics <2.7-fold were predictive of better OS and/or PFS, whereas baseline values of these parameters had no association with patients' survival.…”

Development and Assessment of Novel Predictive Nomograms Based on APRI for Hepatitis B Virus-associated Small Solitary Hepatocellular Carcinoma with Stereotactic Body Radiotherapy

“…Zheng et al have carried out a meta-analysis and reported that an elevated pre-treatment level of NLR or PLR indicated poor outcomes for HCC patients 47 . However, Kinoshita et al, Zhang et al and Zhuang et al believed that pre-treatment NLR and PLR are not correlated to the survival of HCC 22 , 48 , 49 . Our research identified the prognostic factors on HBV-related small solitary HCC since the small HCC patients enrolled in our study were limited to solitary nodule and HBV infection as the only etiological factor.…”

“…The prognostic value of serum inflammation indicators before treatment for liver cancer has been confirmed by studies focus on surgical resection, liver transplantation, target therapy, radiofrequency ablation (RFA),transcatheter arterial chemoembolization (TACE) and selective internal radiation therapy (SIRT) 16 - 21 . However, studies about cases of liver cancer treated with SBRT rarely reported prognostic inflammatory markers, instead, most of which merely focused on NLR and PLR 22 . This article hopes to develop visualized multivariate predictive nomograms and identify more possible novel prognostic indicators for SBRT therapy in hepatitis B-related small solitary HCC by reviewing the existing data.…”