Prognostic effect of body mass index in patients with advanced NSCLC treated with chemoimmunotherapy combinations

Cortellini, Alessio; Ricciuti, Biagio; Vaz, Victor R.; Soldato, Davide; Alessi, Joao; Dall’Olio, Filippo Gustavo; Banna, Giuseppe Luigi; Muthuramalingam, S.; Chan, Samuel; Majem, Margarita; Piedra, A.; Andrini, Elisa; Addeo, Alfredo; Friedlaender, Alex; Facchinetti, Francesco; Gorría, Teresa; Mezquita, Laura; Hoton, Delphine; Lacroix, Valérie; Nana, Frank Aboubakar; Artingstall, James; Comins, Charles; Maïo, Massimo Di; Caglio, Andrea; Cave, Judith; McKenzie, Hayley; Newsom-Davis, Thomas; Evans, Joanne; Tiseo, Marcello; D’Alessio, Antonio; Fulgenzi, Claudia Angela Maria; Besse, Benjamin; Awad, Mark M.; Pinato, David J.

doi:10.1136/jitc-2021-004374

Cited by 21 publications

(27 citation statements)

References 18 publications

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“…In addition, the nutritional status of patients is also an important factor affecting tumor progression. Pre-treatment BMI and albumin levels will affect the prognosis of patients with lung cancer (30)(31)(32). As a new type of nutrition monitoring index, PNI is composed of albumin and lymphocyte count.…”

Section: Discussionmentioning

confidence: 99%

Combined systemic immune-inflammatory index and prognostic nutritional index predict outcomes in advanced non-small cell lung cancer patients receiving platinum-doublet chemotherapy

Fan

Chen

et al. 2023

Front. Oncol.

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BackgroundSystemic immune-inflammatory index (SII) and prognostic nutritional index (PNI) could evaluate the therapeutic efficacy and prognosis in different tumors. However, no studies investigated the SII-PNI score to predict outcomes in non-small cell lung cancer (NSCLC) patients treated with platinum-doublet chemotherapy. The aim of this study was to investigate the SII-PNI score in predicting outcomes in non-small cell lung cancer (NSCLC) patients treated with platinum-doublet chemotherapy.Materials and methodsOur study retrospectively analyzed clinical data from 124 patients with advanced NSCLC receiving platinum-doublet chemotherapy. The SII and PNI were calculated based on peripheral blood cell counts and serum albumin, and the optimal cut-off values were determined using receiver operating characteristic (ROC). All patients were divided into three groups according to the SII-PNI score. The association between the SII-PNI score and the clinicopathological characteristics of the patients was examined. The Kaplan-Meier and Cox regression models were used to assess progression-free survival (PFS)and overall survival (OS).ResultsThere was no significant correlation between SII, PNI at baseline and chemotherapy response in patients with advanced NSCLC (p>0.05). However, after receiving 4 cycles of platinum-doublet chemotherapy, the SII of the SD group (p=0.0369) and PD group (p=0.0286) was significantly higher than that of the PR group. At the same time, the PNI of the SD group (p=0.0112) and the PD group (p=0.0007) was significantly lower than that of the PR group. The PFS of patients with SII-PNI scores of 0, 1, and 2 were 12.0, 7.0, and 5.0 months, and the OS of patients with SII-PNI scores of 0, 1, and 2 were 34.0, 17.0, and 10.5 months, respectively. There was statistical significance among the three groups (all p <0.001). Multivariate analyses showed that the chemotherapy response of progressive disease (PD) (HR, 3.508; 95% CI, 1.546-7.960; p=0.003) and SII-PNI score of 2 (HR, 4.732; 95% CI, 2.561-8.743; p < 0.001) were independently associated with a shorter OS. The uses of targeted drugs (HR, 0.543; 95% CI, 0.329-0.898; p=0.017) and immune checkpoint inhibitors (HR, 0.218; 95% CI, 0.081-0.584; p=0.002) were protective factors for OS in patients with NSCLC.ConclusionCompared with baseline parameters, the correlation between SII, PNI after 4 cycles of chemotherapy and the chemotherapy effect was more significant. The SII-PNI score after 4 cycles of chemotherapy is an effective prognostic biomarker for advanced NSCLC patients treated with platinum-doublet chemotherapy. Patients with a higher SII-PNI score had a worse prognosis.

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Section: Discussionmentioning

confidence: 99%

Combined systemic immune-inflammatory index and prognostic nutritional index predict outcomes in advanced non-small cell lung cancer patients receiving platinum-doublet chemotherapy

Fan

Chen

et al. 2023

Front. Oncol.

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“…After detailed evaluations, 183 studies were excluded because of cut-off values, outcomes, unavailable HR data, or other reasons. Ultimately, nine studies, including 4602 NSCLC patients treated with ICIs, were selected for this metaanalysis [14][15][16][17][18][19][20][21][22] .…”

Section: Literature Searchmentioning

confidence: 99%

“…All nine studies reported the association between BMI and PFS [14][15][16][17][18][19][20][21][22] . The low BMI group included underweight patients (BMI < 18.5 kg/ m 2 ) and normal patients (18.5 ≤ BMI ≤ 24.9 kg/m 2 ).…”

Section: Progression-free Survival For All Studiesmentioning

confidence: 99%

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Impact of BMI on the Survival Outcomes of non-Small Cell Lung Cancer Patients Treated with Immune Checkpoint Inhibitors: A Meta-Analysis

Zhang

Chang

et al. 2023

Preprint

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Objectives ICIs have become the standard treatment for advanced NSCLC patients. Currently, PD-L1 is the most widely useful biomarker to predict ICI efficacy, but the sensitivity and specificity are limited. Therefore, the useful predictive biomarkers of ICI efficacy is urgently needed. BMI is an internationally used measure of body health. Obesity may affect ICI efficacy by changing T cell functions. This meta-analysis aimed to clarify the relationship between BMI and survival outcomes of NSCLC patients treated with ICIs. Methods A systematic review was conducted to identify studies that assessed the association between BMI and survival outcomes in patients treated with ICIs. OS was the primary endpoint, and PFS was the secondary endpoint. Random-effect models or fixed-effect models were utilized to combine study effects according to the Cochran Q and I2 tests. Results Nine studies, including 4602 NSCLC patients treated with ICIs, that met the inclusion criteria were selected for this meta-analysis. There was no significant difference in PFS (HR 0.885; 95% CI 0.777–1.009, p = 0.068) or OS (HR 0.947; 95% CI 0.789–1.137, p = 0.560) between the low BMI group and the high BMI group. However, in the subgroup analysis, compared with normal-weight patients, overweight and obese patients achieved prolonged PFS (HR 0.862; 95% CI 0.760–0.978, p = 0.021) and OS (HR 0.818; 95% CI 0.741–0.902, p＜0.0001). Conclusion Overweight and obese NSCLC patients tend to achieve prolonged survival time with ICI regimens. Further prospective studies are needed to strengthen the association between ICI outcomes and BMI levels.

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“…Obesity-associated in ammation dysregulates immune response, potentially leading profound effects on the toxicity and e cacy of ICIs. Body mass index (BMI) is clinically used to assess body fat in human subjects ( 6 , 7 ). Past studies declared a positive prognostic role of high BMI in NSCLC patients treated by rst-line single agent ICIs-based regimens, whereas con ict result was obtained in the chemoimmunotherapy combinations (6-8 ).…”

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confidence: 99%

Serum cholesterol-riched apolipoprotein-B (apoB) containing lipoproteins predict the response to immune checkpoints inhibitors (ICIs) in non-small cell lung cancer (NSCLC) : A retrospective analysis

Zheng

et al. 2022

Preprint

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Background Lipid metabolism alternations reprogrammed tumor microenvironment (TME) to participate in clinical response to immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC). Body mass index (BMI), clinically used to assess body fat, has been positively correlated with ICIs monotherapy response. Circulating cholesterol is mainly packaged into apolipoproteins B (apoB) in the form of apoB containing lipoproteins, including low-density lipoprotein cholesterol (LDL-C) and remnant cholesterol (RC), which have been regarded as risk factors of tumorigenesis. The association between BMI, lipoproteins, and clinical outcome of ICIs is far from clear. Methods We performed a retrospective case-control analysis of 99 NSCLC patients treated with chemotherapy plus ICIs regimens in the department of oncology and lung cancer center of China-Japan Friendship Hospital between January 2019 to December 2021 and assessed the prognostic value of the BMI, serum lipids, lipoproteins, and apolipoproteins. Efficacy was assessed by response evaluation criteria in solid tumors (RECIST) version 1.1 and evaluated by the ICIs response (durable clinical benefit [DCB] / non-durable benefit [NDB]), best response (active/ non-active) and progression-free survival (PFS). The validation test and the mechanism exploration were performed with public data using bioinformatic methods. Results The contrary results to the ICIs single agents were obtained. BMI ≥ 25 kg/m2 was a risk indicator for NDB, non-active response to ICIs, shorter PFS with the confounders adjusted (OR = 6.06, 95% CI 2.05–19.89, p.val = 0.002; OR = 4.37, 95% CI 1.64–12.43, p.val = 0.004; HR = 3.08, 95% CI 1.63–5.82, p.val < 0.001). High cholesterol-riched apoB containing lipoproteins were risk factors for poor ICIs response. Low RC predicted the better ICIs response and the best response with the satisfied discriminative ability and the well-fitting calibration curves (OR = 0.12, 95%CI 0.02–0.63, p.val = 0.017; OR = 0.22. 95%CI 0.05–0.96, p.val = 0.047). Serum LDL-C predicted the longer PFS of ICIs with the added value to the BMI containing model (HR = 0.43, 95%CI 0.22–0.86, p.val = 0.016). Bioinformatic exploration in the TCGA-LUAD cohort showed that the APOB high group was infiltrated by elevated fibroblasts and other immune-suppressive cells to acquire the stromal barrier and form non-inflamed TME. Functional enrichment analysis indicated that the acquired ICIs resistance might be through the LRP6/5-Wnt-TGF-β axis which required laboratory experiments to verify. Conclusions In the NSCLC population treated with the combination of chemotherapy and ICIs, BMI ≥ 25 kg/m2, the elevated cholesterol-riched apoB containing lipoproteins are promise indicators for the poor ICIs response. Further large-scale validations and experimental explorations are needed.

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Prognostic effect of body mass index in patients with advanced NSCLC treated with chemoimmunotherapy combinations

Cited by 21 publications

References 18 publications

Combined systemic immune-inflammatory index and prognostic nutritional index predict outcomes in advanced non-small cell lung cancer patients receiving platinum-doublet chemotherapy

Combined systemic immune-inflammatory index and prognostic nutritional index predict outcomes in advanced non-small cell lung cancer patients receiving platinum-doublet chemotherapy

Impact of BMI on the Survival Outcomes of non-Small Cell Lung Cancer Patients Treated with Immune Checkpoint Inhibitors: A Meta-Analysis

Serum cholesterol-riched apolipoprotein-B (apoB) containing lipoproteins predict the response to immune checkpoints inhibitors (ICIs) in non-small cell lung cancer (NSCLC) : A retrospective analysis

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