Prognostic value of peripheral blood neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, pan-immune-inflammation value and systemic immune-inflammation index for the efficacy of immunotherapy in patients with advanced gastric cancer

Abstract

Aim: The study aimed to assess the value of pretreatment peripheral blood neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), pan-immune-inflammation value (PIV) and systemic immune-inflammation index (SII) for predicting immunotherapy prognosis and efficacy in advanced gastric cancer (GC). Methods: A total of 84 advanced GC patients received immunotherapy were retrospectively collected. The optimal cut-off values were determined by receiver operating characteristic curves. The univariate and multivariate analysis investigated the effects of NLR, PLR, PIV and SII on patients prognosis. Results: NLR, PLR, PIV and SII had predictive value of efficacy. NLR ≥3.65 was an independent risk factor for worse outcomes. Conclusion: NLR, PLR, PIV and SII have predictive value of efficacy and NLR ≥3.65 suggests a poor prognosis following immunotherapy in advanced GC.

Plain language summary

Immunotherapy can make gastric cancer patients live longer. However, not all patients live longer. We need simple, inexpensive and effective indicators to find patients who can live longer with immunotherapy. Routine blood test is common in our daily lives. Previous studies reported that some indicators in routine blood test can predict the prognosis and efficacy of surgery in gastric cancer patients. But it is not clear in immunotherapy for advanced gastric cancer patients. In our trial, we found that some indicators in routine blood test can help predict the effect of immunotherapy in patients with advanced gastric cancer and screen which patients will live longer with immunotherapy.

Summary points

• Immunotherapy can significantly improve the prognosis of advanced gastric cancer (GC) patients, while the efficacy varies in different populations, and validated metrics are needed to predict efficacy and screen of appropriate populations.

• The commonly used indicators for predicting the efficacy of immunotherapy are based on the histopathology, while there is a relative lack of research from the perspective of the tumor immune microenvironment (TIM) currently.

• In this retrospective study, a total of 84 advanced GC patients received immunotherapy were included and the mean age was 59.24 ± 11.59 years.

• The peripheral blood inflammatory markers neutrophil/lymphocyte ratio (NLR), peripheral blood platelet/lymphocyte ratio (PLR), pan-immune-inflammation value (PIV) and systemic immune-inflammation index (SII) had predictive value for the efficacy of immunotherapy in advanced GC, and the area under the receiver-operating-characteristic (ROC) curve (AUC) of the NLR was 0.849, which was better than that of the PLR, PIV and SII.

• Patients with an NLR ≥ 3.65 had a worse objective response rate (ORR), and patients with an NLR ≥ 3.65, PIV ≥ 499.08 or SII ≥ 693.33 had a worse disease control rate (DCR) after immunotherapy (p < 0.05).

• A performance status (PS) score of 2–3, HER-2 negative status, proficient mismatch repair (pMMR), three or more distant site metastases, abdominal and pelvic metastases, colorectal metastases, the use of immunotherapy in the second line or above, the use of immunotherapy alone, an NLR ≥3.65 and a PLR ≥221.8 were risk factors affecting progression-free survival (PFS; p < 0.05). A PS score of 2–3, pMMR, abdominopelvic metastasis, colorectal metastasis, immunotherapy alone and an NLR ≥3.65 were risk factors affecting overall survival (OS; p < 0.05).

• A PS score of 2–3, pMMR, an NLR ≥ 3.65, the use of immunotherapy in the second line or above and an HER-2 negative status were found to be independent risk factors for worse PFS (p < 0.05). A PS score of 2–3, pMMR, an NLR ≥ 3.65 and abdominal-pelvic metastasis were found to be independent risk factors for worse OS (p < 0.05).

• NLR, PLR, PIV and SII have predictive value of efficacy and NLR ≥3.65 suggests a poor prognosis following immunotherapy in advanced GC.

• This study should be followed up to further evaluate the value of peripheral blood inflammatory markers for predicating efficacy and outcomes of immunotherapy in advanced GC patients by prolonging the observation time and expanding the sample size.

Keywords: :

• advanced gastric cancer
• immunotherapy
• peripheral blood inflammatory marker
• prognostic value

Author contributions

All authors contributed to the method conception and program design of this study. The research data collection, organization and statistical analysis were performed by M Fu, Z Li and X Zhang. The research data and statistical results proofreading was done by J Ma and F Shen. The first draft of the manuscript was written by M Fu and X Zhang. The revision of the manuscript was done by M Fu and Z Li. All the authors participated in the final proofreading of the manuscript and confirmed that there was no relevant conflict of interest.

Financial disclosure

This work was supported by the Fujian Provincial Health Technology Project under Grant 2021QNB020; and Xiamen Medical and Health Guidance Project under Grant 3502Z20214ZD1075 and 3502Z20224ZD1086. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, stock ownership or options and expert testimony.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. This study was approved by Ethics Committee of Zhongshan Hospital, Fudan University (Xiamen Branch) (No. B2023-136).

Data availability statement

The data that support the findings of this study are available from the corresponding author MD F upon reasonable request.

Additional information

Funding

This work was supported by the Fujian Provincial Health Technology Project under Grant 2021QNB020; and Xiamen Medical and Health Guidance Project under Grant 3502Z20214ZD1075 and 3502Z20224ZD1086.