EPSILoN: A Prognostic Score Using Clinical and Blood Biomarkers in Advanced Non–Small-cell Lung Cancer Treated With Immunotherapy

Prelaj, Arsela; Rebuzzi, Sara Elena; Pizzutilo, Pamela; Bilancia, Massimo; Montrone, Michele; Pesola, Francesco; Longo, Vito; Bene, Gabriella Del; Lapadula, Vittoria; Cassano, Flavio; Petrillo, P.; Bafunno, Daniela; Varesano, Niccolò; Lamorgese, V.; Mastrandrea, A.; Ricci, D.; Catino, Annamaria; Galetta, Domenico

doi:10.1016/j.cllc.2019.11.017

Cited by 53 publications

(67 citation statements)

References 50 publications

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“…10,11 Easily-achievable peripheral blood parameters, reflecting an inflamed state, have been investigated as potential biomarkers in different tumors (including RCC), settings, and therapies. [12][13][14][15][16] In the era of ICIs, inflammatory indices have mostly been studied in advanced melanoma and non-small lung cancer patients, [17][18][19][20][21] while fewer and smaller studies have been conducted in patients treated with immunotherapy for genitourinary tumors, [22][23][24][25] including mRCC. 4,[26][27][28][29][30][31][32][33][34][35][36][37][38] The Meet-URO 15 is a multicenter, retrospective study investigating the correlation of baseline peripheral blood inflammatory indices with efficacy and activity outcomes in pre-treated mRCC patients receiving nivolumab in clinical practice.…”

Section: Introductionmentioning

confidence: 99%

Inflammatory indices and clinical factors in metastatic renal cell carcinoma patients treated with nivolumab: the development of a novel prognostic score (Meet-URO 15 study)

et al. 2021

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Background: Despite the survival advantage, not all metastatic renal cell carcinoma (mRCC) patients achieve a long-term benefit from immunotherapy. Moreover, the identification of prognostic biomarkers is still an unmet clinical need. Methods: This multicenter retrospective study investigated the prognostic role of peripheral-blood inflammatory indices and clinical factors to develop a novel prognostic score in mRCC patients receiving at least second-line nivolumab. The complete blood count before the first cycle of therapy was assessed by calculating neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), systemic inflammation index (SII), and systemic inflammation response index (SIRI). Clinical factors included pre-treatment International Metastatic RCC Database Consortium (IMDC) score, line of therapy, and metastatic sites. Results: From October 2015 to November 2019, 571 mRCC patients received nivolumab as second- and further-line treatment in 69% and 31% of cases. In univariable and multivariable analyses all inflammatory indices, IMDC score, and bone metastases significantly correlated with overall survival (OS). The multivariable model with NLR, IMDC score, and bone metastases had the highest c-index (0.697) and was chosen for the developing of the score (Schneeweiss scoring system). After internal validation (bootstrap re-sampling), the final index (Meet-URO score) composed by NLR, IMDC score, and bone metastases had a c-index of 0.691. It identified five categories with distinctive OSs: group 1 (median OS – mOS = not reached), group 2 (mOS = 43.9 months), group 3 (mOS = 22.4 months), group 4 (mOS = 10.3 months), and group 5 (mOS = 3.2 months). Moreover, the Meet-URO score allowed for a fine risk-stratification across all three IMDC groups. Conclusion: The Meet-URO score allowed for the accurate stratification of pretreated mRCC patients receiving nivolumab and is easily applicable for clinical practice at no additional cost. Future steps include its external validation, the assessment of its predictivity, and its application to first-line combinations.

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Section: Introductionmentioning

confidence: 99%

Inflammatory indices and clinical factors in metastatic renal cell carcinoma patients treated with nivolumab: the development of a novel prognostic score (Meet-URO 15 study)

et al. 2021

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“…smoking, ECOG PS, liver metastases, LDH, and NLR) to identify patients with advanced non-small-cell lung cancer who could likely benefit from second-line immunotherapy. 47 The combination of immune-inflammatory biomarkers based on SII, PD-L1, with or without LDH identified herein is a potentially useful tool to identify patients who may benefit from immunotherapy. The results herein may suggest that immunotherapy alone should be the first option for patients with low risk, whereas for those with intermediate risk, immunotherapy is still an option but the participation in trials with investigational combination strategies might be favored; for patients with high risk, alternative options should be contemplated before considering immunotherapy.…”

Section: Discussionmentioning

confidence: 97%

Immune-inflammatory biomarkers as prognostic factors for immunotherapy in pretreated advanced urinary tract cancer patients: an analysis of the Italian SAUL cohort

et al. 2021

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Background: Reliable and affordable prognostic and predictive biomarkers for urothelial carcinoma treated with immunotherapy may allow patients' outcome stratification and drive therapeutic options. The SAUL trial investigated the safety and efficacy of atezolizumab in a real-world setting on 1004 patients with locally advanced or metastatic urothelial carcinoma who progressed to one to three prior systemic therapies. Patients and methods: Using the SAUL Italian cohort of 267 patients, we investigated the prognostic role of neutrophilto-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) and the best performing one of these in combination with programmed death-ligand 1 (PD-L1) with or without lactate dehydrogenase (LDH). Previously reported cut-offs (NLR >3 and NLR >5; SII >1375) in addition to study-defined ones derived from receiver operating characteristic (ROC) analysis were used. Results: The cut-off values for NLR and SII by the ROC analysis were 3.65 (sensitivity 60.4; specificity 63.0) and 884 (sensitivity 64.4; specificity 67.5), respectively. The median overall survival (OS) was 14.7 months for NLR <3.65 [95% confidence interval (CI) 9.9-not reached (NR)] versus 6.0 months for NLR !3.65 (95% CI 3.9-9.4); 14.7 months for SII <884 (95% CI 10.6-NR) versus 6.0 months for SII !884 (95% CI 3.7-8.6). The combination of SII, PD-L1, and LDH stratified OS better than SII plus PD-L1 through better identification of patients with intermediate prognosis (77% versus 48%, respectively). Multivariate analyses confirmed significant correlations with OS and progression-free survival for both the SII þ PD-L1 þ LDH and SII þ PD-L1 combinations. Conclusion:The combination of immune-inflammatory biomarkers based on SII, PD-L1, with or without LDH is a potentially useful and easy-to-assess prognostic tool deserving validation to identify patients who may benefit from immunotherapy alone or alternative therapies.

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“…For example, several peripheral blood parameters-including markers of systemic in ammation such as baseline the neutrophil-to-lymphocyte ratio (NLR), the lymphocyte-to-monocyte ratio (LMR) and the absolute lymphocyte count have been associated with survival in patients with metastatic lung neoplasm treated with the ICIs. 10,11 Neutrophil counts, lymphocyte counts and NLR as the signi cant roles in the in ammatory response also demonstrates its value in various of solid tumors. As people costs much in treatment, a cheaper, readily and more effective potential prognostic markers need to be assisted the prognosis and patient risk strati cation of the lung cancer.…”

Section: Introductionmentioning

confidence: 98%

Prognostic value of neutrophil-to-lymphocyte ratio and location in patients with EGFR mutant metastatic non-small cell lung cancer treated with TKIs

Xie

Tang

et al. 2020

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Background: Targeted therapy with the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has improved the field of metastatic non-small cell lung cancer treatment. Higher neutrophil-to-lymphocyte ratio (NLR) and lower relative lymphocyte counts as inflammatory indicators and associated with worse overall survival and progression free survival (PFS) in several tumor types. Few studies focused on these inflammation markers in context of TKIs eras.Methods: Patients with advanced EGFR mutation NSCLC treated with TKIs were included. Pre-treatment NLR means neutrophil to lymphocyte ratio measured in peripheral blood within one week before treating with TKIs. The baseline clinical characteristics of each group were compared by chi-square and t tests. Cox regression analyses were used to evaluate prognostic value of peripheral blood parameters on progression free survival (PFS). All prognostic factors were explored with multivariable regression.Results: We retrospectively analyzed 221 patients with metastatic NSCLC harboring exon 19 deletion, 21 L858R or rare mutation and receiving TKIs. Finally, a total of 190 patients were analyzed. The optimal cutoff values for pretreatment absolute lymphocyte count (Lym), lymphocyte percentage (Lym%), absolute neutrophil count (Neu), the percentage of neutrophil granulocytes (Neu%) and NLR were 1.625 x 109/L, 18.8%, 3.675a x 109/L, 51.8% and 4.965, respectively. Patients with high neutrophil percent (18.8 months vs 13.0 months, P=0.003), absolute neutrophil counts (12.0 months vs 14.5 months, P=0.014) and NLR (7.0 months vs 15.2 months, P<0.001, one-year PFS Rate, 55.3%, respectively) had worse PFS. In contrast, patients with high absolute lymphocyte counts (16.5 months vs 13.0 months, P=0.012) and lymphocyte percent (15.3 months vs 8.8 months, P<0.001) had a better progression-free-survival. Besides, tumor location was also an important factor for prognosis (14.3 months vs 11.6 months, P=0.003). On multivariate analysis, NLR and primary tumor location were both identified as independent and significantly risk indicators for worse PFS.Conclusion: NLR and primary location are both independent prognostic factors for PFS in patients with metastatic EGFR mutated lung tumor. Whether or not NLR and primary location could be usefulmarkers in efficacy prediction of TKIs in advanced NSCLC calls for further investigation.

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EPSILoN: A Prognostic Score Using Clinical and Blood Biomarkers in Advanced Non–Small-cell Lung Cancer Treated With Immunotherapy

Cited by 53 publications

References 50 publications

Inflammatory indices and clinical factors in metastatic renal cell carcinoma patients treated with nivolumab: the development of a novel prognostic score (Meet-URO 15 study)

Inflammatory indices and clinical factors in metastatic renal cell carcinoma patients treated with nivolumab: the development of a novel prognostic score (Meet-URO 15 study)

Immune-inflammatory biomarkers as prognostic factors for immunotherapy in pretreated advanced urinary tract cancer patients: an analysis of the Italian SAUL cohort

Prognostic value of neutrophil-to-lymphocyte ratio and location in patients with EGFR mutant metastatic non-small cell lung cancer treated with TKIs

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