Published online May 24, 2026. doi: 10.5306/wjco.v17.i5.120140
Revised: March 15, 2026
Accepted: April 10, 2026
Published online: May 24, 2026
Processing time: 93 Days and 20.5 Hours
The lung immune prognostic index (LIPI) has been shown to correlate with prognosis in patients with early-stage non-small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT).
To evaluate the utility of the pretreatment LIPI score as a supplementary prog
Patients with stage I NSCLC who underwent SBRT were retrospectively analyzed. Pretreatment LIPI scores were calculated based on complete blood cell counts and lactate dehydrogenase levels. Patients were stratified into two groups: Good LIPI (0 factors) and poor LIPI (1-2 factors). Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method, and the asso
A total of 68 patients were included. LIPI scores varied across the cohort. Kaplan-Meier analysis demonstrated significantly different prognoses between the two groups (P < 0.05). Significantly longer OS and PFS were observed in patients with good LIPI scores compared to those with poor LIPI scores. Multivariate analysis identified LIPI as an independent prognostic factor for OS.
The pretreatment LIPI score represents a useful prognostic marker for patients with stage I NSCLC treated with SBRT.
Core Tip: The pretreatment lung immune prognostic index (LIPI) serves as a useful, independent prognostic marker for patients with stage I non-small cell lung cancer treated with stereotactic body radiotherapy. Based on routine blood counts and lactate dehydrogenase levels, LIPI effectively stratifies patients into distinct risk groups, with those classified as “Poor LIPI” experiencing significantly shorter median overall survival compared to those with “Good LIPI”. This readily available tool can supplement traditional evaluations to identify high-risk individuals who may benefit from closer monitoring.
- Citation: Gao WH, Luo H, Zhu QY, Jiang Q, Lian LX. Prognostic value of lung immune prognostic index in stage I non-small cell lung cancer treated with stereotactic body radiotherapy: A two-center study. World J Clin Oncol 2026; 17(5): 120140
- URL: https://www.wjgnet.com/2218-4333/full/v17/i5/120140.htm
- DOI: https://dx.doi.org/10.5306/wjco.v17.i5.120140
Lung cancer remains one of the most common malignancies worldwide, with non-small cell lung cancer (NSCLC) accounting for approximately 80%-85% of all cases[1]. Stereotactic body radiotherapy (SBRT) has been established as the standard treatment for patients with early-stage NSCLC who are medically inoperable or refuse surgery. This technique enables highly conformal dose delivery to complex-shaped target volumes while sparing adjacent critical organs such as the spinal cord and heart[2]. In the era of precision oncology, identifying patients most likely to benefit from SBRT is of paramount importance.
Over the past decades, modest yet meaningful progress has been made in the epidemiology, diagnosis, staging, and treatment of cancer. The tumor-node-metastasis (TNM) staging system, developed by the Union for International Cancer Control and the American Joint Committee on Cancer (AJCC), remains the most widely used prognostic indicator[3]. However, previous studies focusing primarily on histopathological features or tumor stage have yielded inconclusive results[4,5]. More recently, accumulating evidence has implicated systemic inflammation in tumor proliferation, metastasis, and therapeutic resistance[6,7]. This has prompted interest in identifying readily accessible inflammatory biomarkers for prognostication.
Several inflammation-related parameters derived from complete blood counts, including white blood cell counts, acute-phase proteins, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio, and lymphocyte-monocyte ratio-have demonstrated prognostic value across various cancer types[8,9]. The derived NLR (dNLR), a surrogate for NLR, has also been reported to correlate with clinical outcomes[10]. To enhance prognostic accuracy, Mezquita et al[11] developed the lung immune prognostic index (LIPI), which combines dNLR > 3 and lactate dehydrogenase (LDH) levels above the upper limit of normal. This composite score has been shown to predict outcomes in advanced NSCLC patients treated with immunotherapy[12,13]. Nevertheless, its prognostic utility in early-stage NSCLC patients undergoing SBRT remains unexplored.
As an easily obtainable biomarker derived from routine blood tests, the LIPI score represents a promising prognostic tool. The present study therefore aims to evaluate the association between pretreatment LIPI scores and survival outcomes in patients with stage I NSCLC treated with SBRT.
Between January 2014 and December 2016, we retrospectively reviewed the hospital records of patients with NSCLC from Henan Provincial People’s Hospital and Henan Cancer Hospital. Patients were eligible for inclusion if they met the following criteria: (1) No prior history of other malignancies; (2) Availability of complete blood cell counts and LDH levels obtained prior to SBRT; (3) Histologically confirmed NSCLC; and (4) Treatment with SBRT alone. All patients were classified as stage I according to the 7th edition of the AJCC TNM classification for lung cancer[14], which was the standard in use during the study period (2014-2016), as the 8th edition was not implemented until 2017/2018.
At the start of treatment, simulation was performed using a slow helical computed tomography (CT) scan extending from the neck to the lower level of the kidneys. Acquired images were post-processed at an Advantage Workstation 4.2 (GE Medical Systems). Two imaging specialists independently reviewed the CT scans. Target volume delineation was performed using CT images; magnetic resonance imaging and positron emission tomography were additionally employed when indicated. SBRT was initiated upon treatment plan approval. All patients received high-energy photon beams from 6 MV linear accelerators, with prescribed doses of 48 Gy in 4 fractions or 50 Gy in 5 fractions.
Following pretreatment complete blood cell count assessment, the dNLR was calculated as: DNLR = absolute neutrophil count/(white blood cell count - absolute neutrophil count). The LIPI score was then generated based on the presence of two factors: DNLR > 3 and LDH level above the upper limit of normal in serum (normal range 109-245 U/L). Patients were stratified into a good LIPI group (0 factors) and a poor LIPI group (1-2 factors).
All quantitative data are presented as mean ± SD. Differences in baseline and clinicopathological characteristics between groups were assessed using the χ2 test. Survival probabilities were estimated using the Kaplan-Meier method, and between-group differences were compared with the log-rank test. Progression-free survival (PFS) was defined as the time from disease diagnosis to disease progression or death from any cause. Overall survival (OS) was defined as the interval from the start of SBRT to the date of death or last follow-up. Multivariable Cox proportional hazards analysis, incorporating the Wald test, was performed to evaluate the prognostic impact of variables including gender, age, Karnofsky performance status (KPS), radiation dose, clinical stage, and LIPI score. A two-tailed P value < 0.05 was considered statistically significant. All statistical analyses were conducted using GraphPad Prism (version 8.0; GraphPad Software Inc., San Diego, CA, United States).
This retrospective analysis comprised 68 consecutive patients with pathologically confirmed stage I NSCLC who were treated at the two institutions between January 2014 and December 2016. Adenocarcinoma constituted the predominant histologic subtype, reflecting the epidemiological distribution observed in early-stage NSCLC populations. The cohort demonstrated a median age of 67 years (range: 46-83 years), with male patients comprising the majority at 54.4% (n = 37). Disease staging was rigorously determined according to the 7th edition of the AJCC TNM staging system, revealing that 31 patients (45.6%) presented with stage IA (T1N0M0) disease, while 37 patients (54.4%) harbored stage IB (T2aN0M0) disease, indicating a slight predominance of more advanced T-stage lesions within this early-stage cohort.
All patients underwent SBRT as definitive local therapy. The prescribed radiation dose was stratified based on tumor characteristics and institutional protocols: 25 patients (36.8%) received a total dose of 48 Gy, whereas the remaining 43 patients (63.2%) were treated to 50 Gy, typically delivered in 4-5 fractions (biologically effective dose ≥ 100 Gy10).
Pretreatment peripheral blood parameters were utilized to calculate the LIPI, yielding a balanced distribution with 35 patients (51.5%) classified into the good LIPI group and 33 patients (48.5%) allocated to the poor LIPI group. Baseline comparative analyses confirmed the absence of significant imbalances between the good and poor LIPI cohorts with respect to age distribution and sex composition (P > 0.05 for both; Table 1), thereby validating the internal comparability of these prognostic groups. The median follow-up duration for the entire study population was 35 months (range: 8-67 months), providing sufficient maturity for survival endpoint assessment while acknowledging that the upper range of follow-up approached 5.6 years, allowing for meaningful long-term outcome evaluation.
| Characteristics | Poor LIPI (n = 35) | Good LIPI (n = 33) | P value |
| Gender | 0.569 | ||
| Male | 20 | 17 | |
| Female | 15 | 16 | |
| Age (years) | 67.7 ± 9.2 | 67.5 ± 10.1 | 0.934 |
| ≤ 65 | 8 | 11 | |
| > 65 | 27 | 22 | |
| Karnofsky score | 0.973 | ||
| 90-100 | 7 | 10 | |
| 70-80 | 28 | 23 | |
| Radiation dose | 0.175 | ||
| 48 Gy/4 Fr | 11 | 14 | |
| 50 Gy/5 Fr | 24 | 19 | |
| Clinical stage | 0.221 | ||
| Ia | 13 | 18 | |
| Ib | 22 | 15 |
The LIPI demonstrated a significant inverse correlation with clinical outcomes, where superior LIPI stratification was associated with improved patient survival. Throughout the observation period, disease progression was documented in 15 patients. Notably, the good LIPI cohort achieved an exceptional median PFS that remained immature and had not been reached by the data cutoff date, in stark contrast to the poor LIPI cohort, which exhibited a substantially abbreviated median PFS of 49.0 months. Kaplan-Meier survival analysis further corroborated these findings, revealing a statistically significant PFS advantage for patients classified in the good LIPI group compared with their counterparts in the poor LIPI group [log-rank test, hazard ratio (HR) = 0.3035, 95% confidence interval (CI): 0.1054-0.8741; P = 0.031; Figure 1A]. At the 3-year landmark, the PFS rates were 84.7% in the good LIPI group vs 80.3% in the poor LIPI group, underscoring the prognostic discriminatory capacity of the LIPI classification system.
During the observation period, mortality events occurred in 14 patients (20.6%), yielding a censored data proportion of 79.4% at the time of analysis. Survival analysis revealed a marked divergence in OS outcomes between the LIPI-stratified cohorts. Specifically, the median OS was not reached in the good LIPI group, whereas the poor LIPI group exhibited a considerably abbreviated median OS of 49.1 months, representing an absolute median survival difference of 15.8 months favoring the good LIPI cohort.
Kaplan-Meier survival analysis with log-rank testing formally confirmed this disparity, demonstrating statistically significant superior OS for patients in the good LIPI group compared with those in the poor LIPI group (HR = 0.2263, 95%CI: 0.0760-0.6733; P = 0.005; Figure 1B). The magnitude of this survival advantage was further quantified at the 3-year landmark: The good LIPI group maintained a robust OS rate of 87.7%, while the poor LIPI group experienced a nearly 30% absolute reduction to 58.0% (absolute difference: 29.7% points). This pronounced divergence in 3-year survival probabilities underscores the substantial prognostic discriminatory capacity of the LIPI classification system in identifying patients at elevated risk for premature mortality following curative-intent SBRT for early-stage NSCLC.
Univariate Cox regression analysis revealed that a poor LIPI score was significantly associated with inferior OS, conferring a 45.3% reduction in the hazard of death compared with the reference group (HR = 0.547, 95%CI: 0.312-0.839, P = 0.004). Notably, this association remained robust after accounting for potential confounders. In contrast, none of the other conventional clinical variables, including patient gender, age at diagnosis, KPS, primary tumor location, or disease clinical stage, demonstrated statistically significant prognostic value for OS in this cohort (all P > 0.05; Table 2).
| Variable | Univariate analysis | Multivariate analysis | ||
| HR (95%CI) | P value | HR (95%CI) | P value | |
| Gender (male vs female) | 2.334 (0.859-6.244) | 0.097 | ||
| Age (≤ 65 vs > 65) | 0.550 (0.263-1.149) | 0.112 | ||
| Karnofsky score (90/100 vs 70/80) | 1.236 (0.395-3.862) | 0.716 | ||
| Radiation dose (48 Gy vs < 50 Gy) | 0.508 (0.227-1.136) | 0.099 | ||
| Clinical stage (Ia vs Ib) | 2.040 (0.732-5.681) | 0.173 | ||
| LIPI scores (good vs poor) | 0.547 (0.312-0.839) | 0.004 | 0.242 (0.104-0.566) | 0.001 |
To further elucidate the independent prognostic contribution of LIPI, multivariate Cox proportional hazards analysis was performed, adjusting for the aforementioned covariates. This analysis definitively identified a good LIPI score as an independent predictor of favorable OS outcomes, with patients in the good LIPI group exhibiting a 75.8% reduction in mortality risk relative to those with poor LIPI scores (adjusted HR = 0.242, 95%CI: 0.104-0.566, P = 0.001). The substantial magnitude of this protective effect, coupled with the highly significant P value and the exclusion of narrower covariates from the final model, underscores the dominant prognostic influence of LIPI in this patient population.
To avoid selection bias, multivariate analysis included clinically relevant variables, such as patient gender, age at diagnosis, KPS, primary tumor location, and clinical stage-regardless of their significance in univariate analysis. The results also identified a good LIPI score as an independent predictor of favorable OS.
The present study provides preliminary evidence that the readily obtainable pretreatment LIPI score may be associated with survival outcomes in patients with stage I NSCLC treated with SBRT. Our findings demonstrate that patients in the good LIPI group experienced significantly better PFS and OS compared with those in the poor LIPI group. These results suggest that the LIPI score may serve as a useful adjunct to conventional clinical parameters in routine prognostic assessment.
The LIPI score was originally developed to predict immunotherapy efficacy in metastatic NSCLC. Subsequent clinical trials have confirmed its prognostic value in advanced NSCLC patients receiving immunotherapy, with favorable LIPI scores consistently associated with superior survival outcomes relative to intermediate or poor scores[11,12,15]. More recently, accumulating evidence has supported the prognostic relevance of pretreatment LIPI scores across various stages and treatment modalities[16-18]. For instance, Zhang et al[17] demonstrated that baseline LIPI score was an independent prognostic marker in locally advanced NSCLC patients treated with radiotherapy, while Su et al[19] reported its utility as a stratification factor in advanced NSCLC patients undergoing concurrent chemoradiotherapy. Despite these advances, data regarding the prognostic significance of LIPI scores in early-stage disease remain limited. The current study addresses this gap by demonstrating that intermediate-to-poor baseline LIPI scores are associated with unfavorable OS in stage I NSCLC patients treated with SBRT. These findings support the potential incorporation of LIPI scores as a prognostic stratification tool in the early-stage NSCLC setting.
The mechanisms underlying the prognostic value of the LIPI score remain under investigation. Systemic inflammation is known to play a critical role in lung cancer progression, and numerous inflammatory biomarkers derived from complete blood counts have been associated with patient outcomes, particularly in early-stage NSCLC. The dNLR, a readily available inflammatory index, has been shown to correlate with poor survival across multiple malignancies, including head and neck, lung, and gastrointestinal cancers. Among medically inoperable early-stage NSCLC patients, a dNLR ≥ 1.99 was identified as an independent prognostic factor[20]. Moreover, combining dNLR (with a cutoff of 3) with immune cell subsets such as CD4+ and CD8+ T lymphocytes and CD68+ macrophages improved prognostic stratification, regardless of treatment modality[21]. Consistent with these findings, the present study adopted a dNLR cutoff of 3 and confirmed its prognostic significance as a component of the LIPI score in early-stage NSCLC. Collectively, these data support dNLR as a key biomarker of systemic inflammation.
LDH, another component of the LIPI score, is a cytosolic enzyme essential to glycolysis. Enhanced glycolytic activity is a hallmark of inflammation[22], and elevated LDH levels have been proposed as a general indicator of inflammatory status[23]. Furthermore, tumor cells depend on glycolytic pathways for survival, and increased glycolysis is now recognized as a core hallmark of cancer[24]. The prognostic role of LDH in solid tumors has been extensively investigated. In NSCLC, elevated pretreatment serum LDH has been consistently associated with poor survival[25]. Moreover, persistently high LDH levels during treatment predict worse outcomes independent of therapeutic response in advanced disease[26]. A multicenter retrospective study from Japan further identified an LDH concentration ≥ 222 U/L as an independent predictor of both overall and disease-free survival in resected NSCLC[27]. Given its established prognostic value, integrating LDH with other biomarkers may enhance the accuracy of cancer prognosis prediction. The LIPI score, which combines dNLR and LDH, represents a practical and inexpensive tool for patient stratification. The present study provides strong evidence supporting the utility of the LIPI score as a prognostic biomarker in NSCLC, enabling the identification of patients at higher risk for poor outcomes. Nevertheless, further investigation is warranted to validate the prognostic performance of the LIPI score across diverse cancer types and treatment settings.
While a poor LIPI score predicts worse survival after SBRT for early-stage NSCLC, it does not predict primary tumor failure. This disconnect suggests that in immunocompromised hosts, even effective local therapy cannot alter systemic progression. Poor LIPI may therefore reflect a persistent, pro-metastatic environment-marked by neutrophil-derived extracellular traps that prime distant niches and elevated LDH that suppresses antitumor immunity while supporting disseminated tumor cells, that endures despite ablation of the primary lesion[28,29]. We hypothesize that poor LIPI identifies patients with functionally systemic disease at presentation, explaining the discordance between local control and survival. Notably, the inclusion of medically inoperable patients-typically older and more frail, may confound this association, as their poor LIPI scores could capture both cancer-specific inflammation and baseline comorbidity.
The main limitations of this study include its retrospective design, as well as the relatively small sample size. Nevertheless, we identified a significant survival benefit associated with good pretreatment LIPI scores in patients with stage I NSCLC treated with SBRT, a finding that has been scarcely reported in prior studies. Future research is warranted to validate these preliminary observations, further refine prognostic stratification based on LIPI, and elucidate the underlying biological mechanisms. Such efforts may ultimately inform more personalized disease management strategies.
In conclusion, our study demonstrates that a good pretreatment LIPI score is associated with improved survival in patients with stage I NSCLC treated with SBRT. The LIPI score holds significant promise as a prognostic biomarker, and its routine assessment prior to SBRT may facilitate meaningful patient stratification and inform clinical decision-making.
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