The Pan-Immune-Inflammation Value in microsatellite instability–high metastatic colorectal cancer patients treated with immune checkpoint inhibitors

Corti, Francesca; Lonardi, Sara; Intini, Rossana; Salati, Massimiliano; Fenocchio, Elisabetta; Belli, Carmen; Borelli, Beatrice; Brambilla, Marta; Prete, Alessandra Anna; Quarà, Virginia; Antista, Maria; Fassan, Matteo; Morano, Federica; Spallanzani, Andrea; Ambrosini, Margherita; Curigliano, Giuseppe; Braud, Filippo de; Zagonel, Vittorina; Fucà, Giovanni; Pietrantonio, Filippo

doi:10.1016/j.ejca.2021.03.043

Cited by 71 publications

(94 citation statements)

References 29 publications

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“…Studies showed that SCLC patients with higher TMB were more likely to benefit from anti-PD-1 inhibitor (19,20). Another factor, ctDNA, was strongly associated with the prognosis of SCLC patients treated with second-line immunotherapy, but the technique [nextgeneration sequencing (NGS)] and expensive cost of TMB and ctDNA evaluations strongly restrict practical clinical applications (13)(14)(15). In the study enrolling SCLC patients with second-or laterline immunotherapy, the median PFS was longer in patients with NLR < 5 than in patients with NLR > 5 at 6 weeks post treatment (16).…”

Section: Discussionmentioning

confidence: 99%

“…Considering routinely hematological parameters reflecting systemic immune and inflammation, PIV is a recently developed biomarker, based on neutrophils, monocytes, platelets, and lymphocytes, and was strongly associated with the clinical outcomes, both PFS and OS, of immunotherapytreated patients with several types of cancers. In colorectal cancer, breast cancer, renal cancer, melanoma, and NSCLC patients treated with immunotherapy, high PIV was a strong predictor for poorer PFS and OS (14,15,20,21). Compared with separate blood cell parameters, PIV might be able to reveal the complexity of the systemic immune and inflammatory status more comprehensively.…”

Section: Discussionmentioning

confidence: 99%

“…Ligorio reported that PIV was an independent predictor of worse OS in patients with HER2-positive advanced breast cancer receiving first-line trastuzumab-pertuzumab biochemotherapy, and PIV outperformed other well-known peripheral blood parameters, such as NLR, PLR, and LMR (20). A pooled analysis also showed that PIV is a new prognostic biomarker in patients with metastatic colorectal cancer treated with first-line therapy and superior to other inflammatory indexes (14,15). Furthermore, compound prognostic scores, combining several parameters, have shown promising ability for the prognostic prediction in immunotherapy-receiving patients (21,22).…”

Section: Introductionmentioning

confidence: 91%

“…Several studies showed that PD-L1 tumor proportion score (TPS), tumor mutational burden (TMB), and circulating tumor DNA (ctDNA) might be potential predictors for ES-SCLC. However, the limitations (technique, cost, and sample restriction) strongly restrict practical clinical applications (13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

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PIV and PILE Score at Baseline Predict Clinical Outcome of Anti-PD-1/PD-L1 Inhibitor Combined With Chemotherapy in Extensive-Stage Small Cell Lung Cancer Patients

et al. 2021

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ObjectivesThe objective of this study is to evaluate whether PIV (Pan-Immune-Inflammation Value) and PILE [a score derived from PIV, lactate dehydrogenase (LDH), and Eastern Cooperative Oncology Group Performance Status (ECOG PS)] can predict clinical outcome of anti-PD-1/PD-L1 inhibitor combined with chemotherapy in patients with extensive-stage (ES) small cell lung cancer (SCLC).MethodsA total of 53 patients with ES-SCLC in the control group of clinical trial (NCT03041311) were included in this study. PIV was calculated as follows: (neutrophil count × platelet count × monocyte count)/lymphocyte count. The PILE scores were composited based on PIV, LDH levels, and ECOG PS. The Kaplan–Meier method and Cox hazards regression models were used for survival analyses. Moreover, the predictive ability of PIV and PILE was validated in an independent real-world group consisting of 84 patients.ResultsPatients in the low PIV group (PIV < median) had longer progression-free survival (PFS) and overall survival (OS) than those in the high PIV group (PIV ≥ median), along with the HR, which was 2.157 and 2.359, respectively (PFS HR 95% CI: 1.181–3.940, p = 0.012; OS HR 95% CI: 1.168–4.762, p = 0.020). High PILE score was observed relating to worse treatment efficacy (disease control rate (DCR): 84.21% vs. 100%, p = 0.047; durable clinical benefit (DCB) rate: 10% vs. 48.5%, p = 0.060) and poor clinical outcome (median PFS: 4.75 vs. 5.53 m, p = 0.043; median OS: 7.13 vs. 15.93 m, p = 0.002). Similar results were obtained about the predictive and prognostic abilities of PIV and PILE scores in the validation group.ConclusionsHigh PIV and high PILE were correlated with worse clinical outcomes in ES-SCLC patients treated with anti-PD-1/PD-L1 inhibitor combined with chemotherapy, reflecting that PIV and PILE might be useful to identify patients unlikely to benefit from anti-PD-1/PD-L1 therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

PIV and PILE Score at Baseline Predict Clinical Outcome of Anti-PD-1/PD-L1 Inhibitor Combined With Chemotherapy in Extensive-Stage Small Cell Lung Cancer Patients

et al. 2021

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“…In the study of Fan et al, an NLR > 5 was associated with poor clinical response to anti-PD-1 therapy in patients with advanced gastric and colorectal cancers 38 . In metastatic MSI-H CRC, the pan-immune-in ammation value, calculated using routine blood test data, is a strong predictor of outcome in patients receiving ICIs 39 . In the current study, an NLR > 3 was also identi ed as a predictor of poor ICI response.…”

Section: Discussionmentioning

confidence: 99%

Inflammatory Conditions Promote Resistance to Immune Checkpoint Inhibitors in High Microsatellite Instability Colorectal Cancer

Sui

Zhang

Tang

et al. 2021

Preprint

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Inflammatory conditions are common complications in colorectal cancer (CRC) and play significant roles in tumor progression and immunosuppression. However, the influence of inflammatory conditions on the tumor response to immune checkpoint inhibitors (ICIs) remains unclear. We included a high microsatellite instability (MSI-H) CRC patient whose primary tumor progressed and liver metastasis regressed after Pembrolizumab treatment. An organoid-T cell coculture model demonstrated an inhibited local immune response instead of systemic immunosuppression. Single-cell RNA sequencing suggested that neutrophils suppress the immune microenvironment, mostly through CTLA-4-associated pathways. A cohort of 73 patients with MSI-H CRC who received ICIs were enrolled, among whom inflammatory conditions were correlated with a poor tumor response. We demonstrated that inflammatory conditions in MSI-H CRCs correlate with resistance to ICIs through neutrophil-associated immunosuppression. Additional CTLA-4 blockade may improve the sensitivity to PD-1 blockade. Clinically, inflammatory conditions could predict a poor response to ICIs in MSI-H CRCs.

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Anti‐PD‐1 therapy for advanced colorectal cancer based on intestinal microecology

Liang

Liu

et al. 2023

J Biochem & Molecular Tox

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To explore the effects of anti‐programmed death‐1 (PD‐1) therapy on advanced colorectal cancer (CRC) based on the intestinal microecology. Ninety‐two patients with advanced CRC were selected. Patients were treated with Apatinib alone or anti PD‐1 treatment combined with Apatinib. The lactulose/mannitol (L/M) value of the urine was detected by high performance liquid chromatography. The changes of intestinal microflora were determined by real‐time fluorescence quantitative PCR. The risk factors were analyzed through multivariate logistic regression analysis. The curative effect of anti PD‐1 treatment combined with the Apatinib treatment (82.61%) was much higher than that of the Apatinib treatment alone (63.04%, p < 0.05). After treatment, the contents of Bifidobacterium, Lactobacillus, and Enterococcus faecalis were higher with lower levels of Escherichia coli in the observation group than the control (p < 0.05). The level of D‐lactic acid and urinary L/M value of the urine in the observation group was lower than that in control after treatment (p < 0.001). The patients had a 3‐year survival rate of 91.30%. Age >60 years old, histological types of mucinous adenocarcinoma and signet ring cell carcinoma, vascular tumor thrombus, nerve invasion, TNM stage of Ⅲ−Ⅳ were independent risk factors, and anti PD‐1 treatment was the protective factor (p < 0.05). In advanced CRC patients receiving anti PD‐1 treatment combined with the Apatinib treatment, the progression of advanced CRC was effectively controlled by maintaining the intestinal microflora balance. Anti PD‐1 therapy can improve the living quality of CRC patients.

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The Pan-Immune-Inflammation Value in microsatellite instability–high metastatic colorectal cancer patients treated with immune checkpoint inhibitors

Cited by 71 publications

References 29 publications

PIV and PILE Score at Baseline Predict Clinical Outcome of Anti-PD-1/PD-L1 Inhibitor Combined With Chemotherapy in Extensive-Stage Small Cell Lung Cancer Patients

PIV and PILE Score at Baseline Predict Clinical Outcome of Anti-PD-1/PD-L1 Inhibitor Combined With Chemotherapy in Extensive-Stage Small Cell Lung Cancer Patients

Inflammatory Conditions Promote Resistance to Immune Checkpoint Inhibitors in High Microsatellite Instability Colorectal Cancer

Anti‐PD‐1 therapy for advanced colorectal cancer based on intestinal microecology

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