Immune checkpoint inhibitor rechallenge in advanced NSCLC: prognostic value of the neutrophil-to-lymphocyte ratio

Introduction

Background

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment landscape of advanced non-small cell lung cancer (NSCLC), providing durable responses and improved survival in a subset of patients. They are now established as a standard of care in both first-line and subsequent-line settings, either as monotherapy or combined with chemotherapy (1-3). Nevertheless, the majority of patients ultimately develop disease progression owing to primary or acquired resistance. This limitation underscores the need for effective salvage strategies, and one such strategy is ICI rechallenge, in which ICI is administered after discontinuation for progression or immune-related adverse events (irAEs) (4-8). While this approach is increasingly applied in real-world practice, robust criteria for patient selection and reliable prognostic biomarkers remain lacking.

Rationale and knowledge gap

ICI rechallenge is based on the rationale that renewed immune activation has the potential to re-establish antitumor efficacy in a subset of patients, despite prior disease progression or treatment discontinuation. Previous studies have examined clinical factors such as ICI-free interval and prior response as potential predictors of benefit (9-11). Inflammation-based biomarkers, such as the neutrophil-to-lymphocyte ratio (NLR) and the lung immune prognostic index (LIPI), have been reported as predictors of ICI efficacy. Several studies have shown their prognostic significance in treatment-naïve patients with NSCLC (12-20). These indices are thought to reflect the balance between host immune competence and systemic inflammation, yet both are profoundly altered by prior ICI exposure and subsequent therapies. Accordingly, it is necessary to evaluate the predictive value of these readily available biomarkers specifically in the rechallenge setting, and to clarify how their prognostic significance may differ from that observed during initial treatment.

Objective

The primary objective of this study was to identify serum biomarkers, especially NLR, as predictors of outcomes in ICI rechallenge for patients with metastatic or recurrent NSCLC who had previously stopped initial ICI therapy due to disease progression or irAEs. As an exploratory analysis, we also examined routinely available blood-based biomarkers such as NLR, measured at initial ICI administration and at the time of rechallenge, to evaluate their potential links to future clinical outcomes in this real-world cohort. We present this article in accordance with the STROBE reporting checklist (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-1094/rc).

Methods

Study design

We conducted a single-center, retrospective cohort study of patients with advanced or recurrent NSCLC who underwent ICI rechallenge between August 2017 and September 2023. Eligible patients had histologically or cytologically confirmed advanced or recurrent NSCLC, with unresectable stage III or IV disease at the start of initial ICI therapy. Rechallenge was defined as re-administration of an ICI following discontinuation of the initial ICI due to disease progression or irAEs. Patients who discontinued initial ICI for other reasons, such as personal preference or completion of a clinical trial protocol, were excluded. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments and was approved by the Institutional Review Board of Sendai Kousei Hospital (No. 7-43). The requirement for individual informed consent was waived due to the retrospective design; an opt-out notice was posted on the hospital website.

Data collection

Clinical, laboratory, and survival data were retrospectively collected from medical records. Collected variables included age, sex, histologic subtype, clinical stage, metastatic sites, programmed death-ligand 1 (PD-L1) expression, oncogenic driver mutation status, Eastern Cooperative Oncology Group performance status (ECOG PS), and details of prior systemic therapies. PD-L1 expression was assessed using the 22C3 pharmDx assay. The course of initial ICI therapy, including duration, best response, and reason for discontinuation, was recorded. Laboratory data were extracted at two time points: immediately before the initial ICI and immediately before the rechallenge ICI. Tumor responses were assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. irAEs were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Follow-up was completed in November 2024. For both the initial ICI and the rechallenge ICI, progression-free survival (PFS) was defined as the time from the start of each ICI treatment to radiographic or clinical disease progression or death, whichever occurred first. Overall survival (OS) was defined separately for each setting as the time from the start of the corresponding ICI treatment to death from any cause or last follow-up. Unless otherwise specified, references to PFS and OS in this manuscript refer to outcomes from the time of ICI rechallenge.

Statistical analysis

PFS and OS were estimated using the Kaplan-Meier method, and survival differences between groups were evaluated with the log-rank test. Quantitative variables were analyzed as continuous variables where appropriate. Subgroup analyses were conducted based on clinical factors, such as age and ECOG PS, as well as serological markers. Cases with unknown PD-L1 expression were included in all overall analyses. For PD-L1-stratified comparisons, these cases were excluded from subgroup analyses. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models for both univariate and multivariate analyses. Variables for multivariate models were selected based on both univariate P values (<0.10) and clinical relevance from prior literature. All inflammation-based biomarkers used in the analyses were classified using cutoff values commonly employed in previously published immunotherapy studies, rather than being optimized within this study’s cohort. Receiver operating characteristic (ROC) curve analysis was not conducted due to the limited sample size. Inflammation-based biomarkers were calculated using standard definitions as follows: the NLR was calculated as the absolute neutrophil count divided by the absolute lymphocyte count; the LIPI was defined using the derived neutrophil-to-lymphocyte ratio (dNLR) and lactate dehydrogenase (LDH) levels, where dNLR was calculated as the neutrophil count divided by the difference between the white blood cell count and neutrophil count, and LIPI was categorized as 0 [dNLR <3 and LDH ≤ the upper limit of normal (ULN)], 1 (dNLR ≥3 or LDH >ULN), or 2 (dNLR ≥3 and LDH >ULN); the C-reactive protein-to-albumin ratio (CAR) was calculated as the serum C-reactive protein level divided by the serum albumin level; the monocyte-to-lymphocyte ratio (MLR) was calculated as the absolute monocyte count divided by the absolute lymphocyte count; the platelet-to-lymphocyte ratio (PLR) was calculated as the platelet count divided by the lymphocyte count; the prognostic nutritional index (PNI) was calculated as 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (/mm³); and the systemic inflammation response index (SIRI) was calculated as (neutrophil count × monocyte count) divided by the lymphocyte count. Paired changes in inflammation-based biomarkers between initial and rechallenge ICI were compared using the Wilcoxon signed-rank test for paired data. Missing data were addressed by excluding one patient for whom blood test data immediately prior to the initial ICI administration were unavailable; all other analyses were conducted with complete cases. All statistical analyses were performed using Easy R (EZR), with a two-sided P value <0.05 considered statistically significant.

Results

Patient characteristics

A total of 33 patients with advanced or recurrent NSCLC were analyzed. The median age at ICI rechallenge was 65 years (range, 36–79 years). Most patients were male (78.8%) and had an ECOG PS of 1 at rechallenge (78.8%). Adenocarcinoma was the predominant histology (57.6%). Tumor PD-L1 expression was ≥1% in 66.6%, <1% in 24.2%, and unknown in 9.1%. EGFR mutations were absent in 90.9% of patients. All patients had received anti-PD-1 inhibitor-based therapy as initial ICI; none had received atezolizumab. The median number of systemic treatment lines before rechallenge was 3 (range, 2–9). At rechallenge, all patients received ICI monotherapy: 39.4% received atezolizumab, 21.2% pembrolizumab, and 39.4% nivolumab. Thirteen patients (39.4%) switched from an initial anti-PD-1 to an anti-PD-L1 agent, while 20 (60.6%) received a PD-1 inhibitor again, all by cross-switching between nivolumab and pembrolizumab; no patient was re-treated with the same PD-1 agent. No patient received combination chemo-immunotherapy or dual ICI at rechallenge (Table 1).

Efficacy outcomes and main results: prognostic biomarkers at ICI rechallenge

During initial ICI therapy, median PFS and OS were 8.1 months (95% CI: 5.1–9.7) and 28.3 months (95% CI: 24.4–41.9), respectively, with an objective response rate (ORR) of 45.5%. Upon ICI rechallenge, the median follow-up period was 27.6 months. Among 33 patients, disease progression after ICI rechallenge occurred in 28 patients (84.8%), and 29 patients (87.9%) died. Median PFS and OS were 2.2 months (95% CI: 1.9–3.9) and 6.6 months (95% CI: 5.9–15.7), respectively, with an ORR of 12.1% (Figure 1). In univariate analyses, NLR <4 at rechallenge was significantly associated with improved outcomes (PFS: HR 0.30, P=0.01; OS: HR 0.25, P=0.001). Additional factors associated with longer OS included ECOG PS 0, PLR <200, and C-reactive protein (CRP) <10 mg/dL (Table 2).

Figure 1 Kaplan-Meier curves for survival outcomes during ICI rechallenge. Median PFS was 2.2 months (95% CI: 1.9–3.9), and median OS was 6.6 months (95% CI: 5.9–15.7). The number of patients at risk is shown below each plot. CI, confidence interval; ICI, immune checkpoint inhibitor; OS, overall survival; PFS, progression-free survival.

In multivariate analysis, NLR <4 at ICI rechallenge remained independently associated with better OS (HR 0.32; P=0.02), whereas ECOG PS and ICI rechallenge pattern were not statistically significant (Table 3). Kaplan-Meier curves confirmed that patients with NLR <4 had significantly longer PFS and OS at rechallenge (Figure 2). Moreover, NLR at the time of initial ICI was also evaluated using a cutoff of 3. Patients with baseline NLR <3 (n=16) had numerically longer PFS (9.9 vs. 7.1 months; P=0.54) and OS (37.9 vs. 26.8 months; P=0.07) compared with those with NLR ≥3 (n=16), although these differences did not reach statistical significance.

Figure 2 Kaplan-Meier curves for PFS (A) and OS (B) according to NLR at ICI rechallenge. Patients with NLR <4 demonstrated significantly longer PFS (median, 3.94 months) compared to those with NLR ≥4 (median, 2.00 months; P=0.01). Similarly, patients with NLR <4 showed significantly better OS (median, 16.20 months) than those with NLR ≥4 (median, 5.93 months; P=0.001). The number of patients at risk is shown below each plot. ICI, immune checkpoint inhibitor; NLR, neutrophil-to-lymphocyte ratio; OS, overall survival; PFS, progression-free survival.

Exploratory analysis

We further evaluated dynamic changes in biomarker profiles between initial ICI and rechallenge. Several indices shifted toward a more pro-inflammatory and catabolic status: NLR increased (3.0→4.5, P=0.004), MLR increased (0.28→0.42, P=0.01), and SIRI increased (1.30→1.88, P =0.01), whereas albumin decreased (3.70→3.40 g/dL, P=0.003) and PNI decreased (44.20→40.10, P=0.004) (Table 4).

Safety

Regarding safety, irAEs occurred in 16 patients (51.5%) during initial ICI therapy and in 11 patients (33.3%) during rechallenge (Table 5). The most frequent irAEs during initial treatment were skin rash (24.2%), pneumonitis (15.2%), hepatotoxicity (12.1%), colitis (6.1%), and endocrinopathies (3.0%). During rechallenge, pneumonitis (12.1%) remained the most frequent, followed by colitis (9.1%), hepatotoxicity (6.1%), and both skin rash and endocrinopathies (3.0%). Myocarditis and cytokine release syndrome were each observed in 3.0% of patients exclusively during rechallenge. One treatment-related death due to pneumonitis occurred during rechallenge (Table 5).

Discussion

Key findings

In this study, the clinical efficacy of ICI rechallenge was modest, with lower response rates and shorter survival compared to initial ICI therapy, consistent with prior reports. The key finding, however, was that NLR measured immediately before rechallenge strongly predicted outcomes: patients with NLR <4 experienced significantly longer PFS and OS, and NLR <4 remained an independent prognostic factor for OS in multivariate analysis (HR 0.242; P=0.008). Moreover, analysis of NLR at the time of initial ICI showed only a trend, without statistical significance, toward longer OS in patients with NLR <3. In contrast, exploratory analyses demonstrated a clear and statistically significant rise in NLR between the initial and rechallenge settings (3.0→4.5), reflecting progressive systemic inflammation. Taken together, these observations suggest that the prognostic threshold of NLR may shift upward over time, possibly reflecting dynamic changes in the systemic inflammatory environment between the initial and rechallenge settings. Accordingly, while NLR <3 may have been relevant at initial ICI, an NLR cutoff of 4 emerged as more strongly predictive at rechallenge, underscoring the utility of NLR as a prognostic marker in the rechallenge setting.

Strengths and limitations

The major strength of this study is its focused evaluation of blood-based prognostic biomarkers in the ICI rechallenge setting, with particular emphasis on NLR. By assessing laboratory profiles at both initial ICI treatment and at rechallenge, we were able to document dynamic changes in systemic inflammation. This longitudinal approach allowed us to demonstrate that a lower NLR at rechallenge (<4) was consistently associated with longer PFS and OS and remained an independent prognostic factor for OS in multivariate analysis. However, several limitations should be acknowledged. First, the retrospective, single-center design and small sample size may limit both statistical power and generalizability. This reflects the relatively small number of patients undergoing ICI rechallenge in routine practice, a population underrepresented in prospective trials. Accordingly, this study should be regarded as hypothesis-generating, and its findings require validation in larger multicenter cohorts. Second, the study population was heterogeneous, including patients who switched ICI agents and those who discontinued initial ICI due to irAEs rather than disease progression, potentially introducing confounding. Third, the evidence supporting the cutoff values for NLR and other inflammatory markers in this retrospective analysis was limited. While thresholds were determined with reference to prior studies, selection bias cannot be entirely excluded. Despite these limitations, the identification of NLR as an independent prognostic factor and the paired evaluation of biomarkers at two distinct treatment time points enhance the clinical relevance of this study and provide a basis for future prospective research. Subsequent investigations should aim to establish evidence-based cutoff values for inflammation-based biomarkers and assess their longitudinal changes in larger, well-designed cohorts systematically.

Comparison with similar research

Published studies consistently show that the efficacy of ICI rechallenge in advanced NSCLC is modest. A recent meta-analysis reported a pooled ORR of 10% (95% CI: 4–18%), a disease control rate (DCR) of 50% (95% CI: 37–62%), a median PFS of 3.0 months (95% CI: 2.1–3.9), and a median OS of 13.1 months (95% CI: 10.2–16.10) (6). As a prospective study, the WJOG9616L trial by Akamatsu et al. reported an ORR of 8.5% and a median PFS of 2.6 months for nivolumab retreatment (9). Overall, these findings suggest that ICI rechallenge, whether with the same or different agents, offers limited benefit in unselected NSCLC populations. When directly compared with our findings, the magnitude of benefit in our cohort was largely in line with these prior reports, with ORR (12.1%) and median PFS (2.2 months) falling within the lower range of published values. The shorter OS observed in our study (6.6 months) compared to the pooled estimate from meta-analysis (13.1 months) may reflect the heavily pretreated nature of our population. Factors such as NLR, LIPI, serum albumin, CAR, and modified Glasgow Prognostic Score (mGPS) have previously been reported to correlate with ICI treatment (21). In a retrospective cohort study by Musaelyan et al., ICI rechallenge in advanced NSCLC was associated with an OS benefit, and a low NLR was identified as an independent favorable prognostic factor for both PFS and OS, with an NLR cut-off of 3.8 closely aligning with that used in our study. In a subsequent analysis by the same group, evaluating ICI rechallenge combined with metronomic cyclophosphamide with or without bevacizumab, low NLR emerged as an independent negative predictor of outcomes. Collectively, these findings support the reproducibility of NLR as a prognostic marker across different ICI rechallenge strategies (22,23). Similarly, a large multicenter retrospective study of 144 patients undergoing PD-1/PD-L1 rechallenge reported that longer survival was associated with favorable clinical features, including good PS, a treatment-free interval, and non-progression-related discontinuation of initial ICI. Although only performance status remained significant in multivariate analysis, these findings underscore the importance of clinical context in determining outcomes after ICI rechallenge (24). In our systematic evaluation of inflammation- and nutrition-based biomarkers, NLR at the time of rechallenge independently predicted longer PFS and OS. Given its accessibility and well-established role in immuno-oncology, NLR is a practical marker to improve patient selection for ICI rechallenge.

Explanations of findings

After previous ICI therapy, tumors that exhibit immune-evasive characteristics, such as losing antigen-presenting molecules and increased expression of checkpoint ligand, are more likely to persist, while prolonged antigen exposure also drives T-cell exhaustion (25). These combined factors hinder effective T-cell-mediated attack upon ICI rechallenge, thus diminishing the therapy’s effectiveness compared to initial treatment. Nevertheless, a subset of patients still derive benefit, and the NLR may help identify them. NLR is a systemic inflammatory marker that summarizes the balance between myeloid-driven inflammation and adaptive T-cell immunity (26). Additionally, measuring NLR immediately before ICI rechallenge provides the most relevant prediction of benefit, as it directly indicates the patient’s current systemic inflammatory status after previous treatments and disease progression. This explains why pre-rechallenge NLR emerged as a robust prognostic factor for both PFS and OS in our cohort and highlights its potential utility for refining patient selection in clinical practice.

Implications and actions needed

This study highlights that assessing the patient's immediate pre-rechallenge inflammatory and nutritional status, as reflected by markers like NLR, can offer crucial insights into the likelihood of therapeutic benefit. Given its simplicity and routine availability in clinical practice, NLR could serve as a practical tool for patient stratification and selection for ICI rechallenge. However, recognizing the retrospective, single-center design and limited sample size of our study, these findings should be regarded as hypothesis-generating. To translate these observations into actionable clinical guidelines, future investigations are essential. Specifically, larger, multicenter, prospective clinical trials are warranted to validate the prognostic utility of NLR and to establish evidence-based cutoff values. Furthermore, these studies should aim to systematically assess longitudinal changes in inflammation-based biomarkers and explore their incorporation into comprehensive predictive scores. Such efforts will be crucial to refine patient selection strategies, optimize treatment sequencing, and ultimately improve outcomes for patients undergoing ICI rechallenge.

Conclusions

In conclusion, this study shows that while the clinical efficacy of ICI rechallenge is limited in heavily pretreated NSCLC, the NLR measured immediately prior to rechallenge holds promise as a readily available prognostic biomarker. These observations underscore the dynamic nature of systemic inflammation and its potential to influence the response to subsequent immunotherapy. While our study offers valuable initial insights, especially regarding the role of NLR in predicting outcomes of ICI rechallenge, these findings highlight the importance of systemic inflammation in shaping outcomes of subsequent immunotherapy and suggest that NLR can support patient selection for ICI rechallenge. Considering the retrospective, single-center design and small sample size, our results should be considered hypothesis-generating. Prospective multicenter studies are needed to validate NLR, establish optimal cut-off values, and explore its integration into predictive models that include dynamic changes in inflammation- and nutrition-based markers. These efforts will be crucial to optimizing patient selection and improving outcomes with ICI rechallenge in advanced NSCLC.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-1094/rc

Data Sharing Statement: Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-1094/dss

Peer Review File: Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-1094/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-1094/coif). Y.T. reports personal honoraria for lectures or educational activities from AstraZeneca, Chugai Pharma, Pfizer, Taiho Pharmaceutical, Kyowa Kirin, Bristol-Myers Squibb, Ono Pharmaceutical, and MSD K.K. J.S. reports personal honoraria for lectures or educational activities from AstraZeneca, MSD, Chugai Pharmaceutical, and Kyowa Kirin. S.Y. reports personal honoraria for lectures or educational activities from AstraZeneca, Novartis, Sanofi, GSK, and Nippon Boehringer Ingelheim. Shunichi Sugawara reports institutional research grants from AnHeart, AstraZeneca, Chugai Pharma, MSD, Daiichi Sankyo, Bristol-Myers Squibb, Nippon Boehringer Ingelheim, AbbVie, Amgen, Taiho Pharmaceutical, Parexel International, PPD, IQVIA, Novocure, Pharma Mar, GSK, and Delta-Fly Pharma; and personal honoraria for lectures or educational activities from AstraZeneca, Chugai Pharma, Ono Pharmaceutical, Bristol-Myers Squibb, MSD, Nippon Boehringer Ingelheim, Pfizer, Taiho Pharmaceutical, Eli Lilly, Novartis, Kyowa Kirin, Takeda, Nippon Kayaku, Merck, Amgen, Daiichi Sankyo, Thermo Fisher Scientific, Sysmex, and Eisai. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was approved by the Institutional Review Board of Sendai Kousei Hospital (No. 7-43), and conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The requirement for individual informed consent was waived due to the retrospective design; an opt-out notice was posted on the hospital website.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Jeon H, Wang S, Song J, et al. Update 2025: Management of Non‑Small-Cell Lung Cancer. Lung 2025;203:53. [Crossref] [PubMed]
2. de Castro G Jr, Kudaba I, Wu YL, et al. Five-Year Outcomes With Pembrolizumab Versus Chemotherapy as First-Line Therapy in Patients With Non-Small-Cell Lung Cancer and Programmed Death Ligand-1 Tumor Proportion Score ≥ 1% in the KEYNOTE-042 Study. J Clin Oncol 2023;41:1986-91. [Crossref] [PubMed]
3. Garassino MC, Gadgeel S, Speranza G, et al. Pembrolizumab Plus Pemetrexed and Platinum in Nonsquamous Non-Small-Cell Lung Cancer: 5-Year Outcomes From the Phase 3 KEYNOTE-189 Study. J Clin Oncol 2023;41:1992-8. [Crossref] [PubMed]
4. Livanou ME, Nikolaidou V, Skouras V, et al. Efficacy of NSCLC Rechallenge with Immune Checkpoint Inhibitors following Disease Progression or Relapse. Cancers (Basel) 2024;16:1196. [Crossref] [PubMed]
5. Gang X, Yan J, Li X, et al. Immune checkpoint inhibitors rechallenge in non-small cell lung cancer: Current evidence and future directions. Cancer Lett 2024;604:217241. [Crossref] [PubMed]
6. Feng Y, Tao Y, Chen H, et al. Efficacy and safety of immune checkpoint inhibitor rechallenge in non-small cell lung cancer: A systematic review and meta-analysis. Thorac Cancer 2023;14:2536-47. [Crossref] [PubMed]
7. Lin G, Wang Z, Chu Q, et al. Rechallenge of immune checkpoint inhibitors in advanced non-small cell lung cancer. Thorac Cancer 2024;15:419-26. [Crossref] [PubMed]
8. Cai Z, Zhan P, Song Y, et al. Safety and efficacy of retreatment with immune checkpoint inhibitors in non-small cell lung cancer: a systematic review and meta-analysis. Transl Lung Cancer Res 2022;11:1555-66. [Crossref] [PubMed]
9. Akamatsu H, Teraoka S, Takamori S, et al. Nivolumab Retreatment in Non-Small Cell Lung Cancer Patients Who Responded to Prior Immune Checkpoint Inhibitors and Had ICI-Free Intervals (WJOG9616L). Clin Cancer Res 2022; Epub ahead of print. [Crossref]
10. Takahara Y, Tanaka T, Ishige Y, et al. Efficacy and predictors of rechallenge with immune checkpoint inhibitors in non-small cell lung cancer. Thorac Cancer 2022;13:624-30. [Crossref] [PubMed]
11. Xu Z, Hao X, Yang K, et al. Immune checkpoint inhibitor rechallenge in advanced or metastatic non-small cell lung cancer: a retrospective cohort study. J Cancer Res Clin Oncol 2022;148:3081-9. [Crossref] [PubMed]
12. Platini H, Ferdinand E, Kohar K, et al. Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio as Prognostic Markers for Advanced Non-Small-Cell Lung Cancer Treated with Immunotherapy: A Systematic Review and Meta-Analysis. Medicina (Kaunas) 2022;58:1069. [Crossref] [PubMed]
13. Mezquita L, Auclin E, Ferrara R, et al. Association of the Lung Immune Prognostic Index With Immune Checkpoint Inhibitor Outcomes in Patients With Advanced Non-Small Cell Lung Cancer. JAMA Oncol 2018;4:351-7. [Crossref] [PubMed]
14. Dai M, Wu W. Prognostic role of C-reactive protein to albumin ratio in cancer patients treated with immune checkpoint inhibitors: a meta-analysis. Front Oncol 2022;28:OF1-7. [Crossref] [PubMed]
15. Wu J, Wang H, Yang R, et al. Prognostic significance of the modified Glasgow Prognostic Score in NSCLC patients undergoing immune checkpoint inhibitor therapy: a meta-analysis. Front Oncol 2024;14:1449853. [Crossref] [PubMed]
16. Tong W, Xu H, Tang J, et al. Inflammatory factors are associated with prognosis of non-small cell lung cancer patients receiving immunotherapy: a meta-analysis. Sci Rep 2024;14:26102. [Crossref] [PubMed]
17. Onodera R, Chiba S, Nihei S, et al. High level of C-reactive protein as a predictive factor for immune-related adverse events of immune checkpoint inhibitors in non-small cell lung cancer: a retrospective study. J Thorac Dis 2023;15:4237-47. [Crossref] [PubMed]
18. Araki T, Tateishi K, Sonehara K, et al. Clinical utility of the C-reactive protein:albumin ratio in non-small cell lung cancer patients treated with nivolumab. Thorac Cancer 2021;12:603-12. [Crossref] [PubMed]
19. Huangfu Y, Chang F, Zhang F, et al. Monocytes-to-lymphocytes ratio increases the prognostic value of circulating tumor cells in non-small cell lung cancer: a prospective study. Transl Cancer Res 2024;13:3589-98. [Crossref] [PubMed]
20. Ezdoglian A, Tsang-A-Sjoe M, Khodadust F, et al. Monocyte-related markers as predictors of immune checkpoint inhibitor efficacy and immune-related adverse events: a systematic review and meta-analysis. Cancer Metastasis Rev 2025;44:35. [Crossref] [PubMed]
21. Guo Y, Wei L, Patel SH, et al. Serum Albumin: Early Prognostic Marker of Benefit for Immune Checkpoint Inhibitor Monotherapy But Not Chemoimmunotherapy. Clin Lung Cancer 2022;23:345-55. [Crossref] [PubMed]
22. Musaelyan AA, Odintsova SV, Musaelyan KA, et al. Predictive markers of response to immune checkpoint inhibitor rechallenge in metastatic non-small cell lung cancer. Explor Target Antitumor Ther 2024;5:1271-88. [Crossref] [PubMed]
23. Musaelyan AA, Odintsova SV, Urtenova MA, et al. Efficacy of immune checkpoint inhibitors rechallenge and metronomic cyclophosphamide with or without bevacizumab in metastatic nonsmall cell lung cancer. Anticancer Drugs 2025;36:583-91. [Crossref] [PubMed]
24. Gobbini E, Toffart AC, Pérol M, et al. Immune Checkpoint Inhibitors Rechallenge Efficacy in Non-Small-Cell Lung Cancer Patients. Clin Lung Cancer 2020;21:e497-510. [Crossref] [PubMed]
25. Sharma P, Hu-Lieskovan S, Wargo JA, et al. Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy. Cell 2017;168:707-23. [Crossref] [PubMed]
26. Zahorec R. Neutrophil-to-lymphocyte ratio, past, present and future perspectives. Bratisl Lek Listy 2021;122:474-88. [Crossref] [PubMed]