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Jia SZ, Yang XJ, Yang D, Wang R, Yang X, Huang MN, An JS. Low pretreatment prognostic nutritional index predicts unfavorable survival in stage III-IVA squamous cervical cancer undergoing chemoradiotherapy. BMC Cancer 2025; 25:377. [PMID: 40022054 PMCID: PMC11871652 DOI: 10.1186/s12885-025-13752-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2024] [Accepted: 02/17/2025] [Indexed: 03/03/2025] Open
Abstract
BACKGROUND To investigate potential predictive factors and assess the utility of systemic inflammatory and nutritional indexes as prognostic indicators for survival in patients with FIGO stage III-IVA squamous cervical cancer (squamous HR-LACC) treated with concurrent chemoradiotherapy. METHODS We included consecutive patients with PET-CT diagnosed squamous HR-LACC undergoing curative chemoradiotherapy from November 2016 to April 2024. We systematically reviewed data pertaining to pretreatment clinicopathologic characteristics, hematological parameters, and treatment specifics. A range of composite inflammatory and nutritional indices were calculated, including the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, systemic immune-inflammation index, systemic inflammation response index, pan-immune-inflammation value, and prognostic nutritional index (PNI). X-Tile software was utilized to establish optimal cut-off values based on progression-free survival (PFS). Both univariate and multivariate Cox regression analyses were conducted to identify factors associated with PFS and overall survival (OS). RESULTS Among 157 patients (median age 55) included, 136 had lymph node involvement, and 45 had para-aortic metastasis. After a median follow-up of 35 months, 47 patients had disease progression, and 22 died, yielding 3-year PFS and OS rates of 66.2% and 82.0%, respectively. Multivariate analysis revealed that low SCC-Ag (HR: 1.518, 95% CI: 1.067-2.159, p = 0.020), para-aortic lymph node involvement (HR: 1.864, 95% CI: 1.020-3.408, p = 0.043), and low PNI (HR: 1.477, 95% CI: 1.105-1.975, p = 0.009) were independently associated with worse PFS, whereas low PNI emerged as the sole independent risk factor for diminished OS (HR = 1.525, 95% CI: 1.002-2.323, p = 0.049). CONCLUSIONS PNI, a readily obtainable metric based on albumin and lymphocyte count, can serve as a predictor of survival in HR-LACC patients undergoing concurrent chemoradiotherapy. Further research is necessary to ascertain whether optimizing pretreatment nutritional status, a modifiable factor, can enhance outcomes in these high-risk patients.
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Affiliation(s)
- Shuang-Zheng Jia
- Department of Gynecologic Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China
| | - Xue-Jiao Yang
- Department of Gynecologic Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China
| | - Duan Yang
- Department of Gynecologic Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China
| | - Rui Wang
- Department of Gynecologic Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China
| | - Xi Yang
- Department of Gynecologic Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China
| | - Man-Ni Huang
- Department of Gynecologic Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China
| | - Ju-Sheng An
- Department of Gynecologic Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China.
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Zeng D, Wen NY, Wang YQ, Cheng NS, Li B. Prognostic roles nutritional index in patients with resectable and advanced biliary tract cancers. World J Gastroenterol 2025; 31:97697. [PMID: 39958446 PMCID: PMC11752707 DOI: 10.3748/wjg.v31.i6.97697] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Revised: 10/24/2024] [Accepted: 12/16/2024] [Indexed: 01/10/2025] Open
Abstract
BACKGROUND Biliary tract cancer (BTC) is a rare, aggressive malignancy with increasing incidence and poor prognosis. Identifying preoperative prognostic factors is crucial for effective risk-benefit assessments and patient stratification. The prognostic nutritional index (PNI), which reflects immune-inflammatory and nutritional status, has shown prognostic value in various cancers, but its significance in BTC remains unclear. AIM To assess the prognostic value of the preoperative PNI in BTC patients, with a focus on overall survival (OS) and disease-free survival (DFS). METHODS Comprehensive searches were conducted in the PubMed, EMBASE, and Web of Science databases from inception to April 2024. The primary outcomes of interest focused on the associations between the preoperative PNI and the prognosis of BTC patients, specifically OS and disease-free survival (DFS). Statistical analyses were conducted via STATA 17.0 software. RESULTS Seventeen studies encompassing 4645 patients met the inclusion criteria. Meta-analysis revealed that a low PNI was significantly associated with poorer OS [hazard ratio (HR) 1.91, 95%CI: 1.59-2.29; P < 0.001] and DFS (HR 1.93, 95%CI: 1.39-2.67; P < 0.001). Subgroup analyses revealed consistent results across BTC subtypes (cholangiocarcinoma and gallbladder cancer) and stages (resectable and advanced). Sensitivity analyses confirmed the robustness of these findings, and no significant publication bias was detected. CONCLUSION This study demonstrated that a low preoperative PNI predicts poor OS and DFS in BTC patients, highlighting its potential as a valuable prognostic tool. Further prospective studies are needed to validate these findings and enhance BTC patient management.
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Affiliation(s)
- Di Zeng
- Division of Biliary Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
- Research Center for Biliary Diseases, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Ning-Yuan Wen
- Division of Biliary Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
- Research Center for Biliary Diseases, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Yao-Qun Wang
- Division of Biliary Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
- Research Center for Biliary Diseases, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Nan-Sheng Cheng
- Division of Biliary Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
- Research Center for Biliary Diseases, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Bei Li
- Division of Biliary Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
- Research Center for Biliary Diseases, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
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Santoni M, Mollica V, Rizzo A, Massari F. Dynamics of resistance to immunotherapy and TKI in patients with advanced renal cell carcinoma. Cancer Treat Rev 2025; 133:102881. [PMID: 39799795 DOI: 10.1016/j.ctrv.2025.102881] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2024] [Revised: 01/03/2025] [Accepted: 01/05/2025] [Indexed: 01/15/2025]
Abstract
Immune-based combinations are the cornerstone of the first-line treatment of metastatic renal cell carcinoma patients, leading to outstanding outcomes. Nevertheless, primary resistance and disease progression is a critical clinical challenge. To properly address this issue, it is pivotal to understand the mechanisms of resistance to immunotherapy and tyrosine kinase inhibitors, that tumor eventually develop under treatment. In this review of the literature, we aim at exploring resistance mechanisms arising in patients treated with first-line immune-based combinations in order to understand the biological pattern that should be investigated to overcome them. In more detail, mechanisms of resistance to nivolumab and pembrolizumab are divided into intrinsic to cancer cells and extrinsic (stromal or immune cells). Regarding axitinib, the increased expression of Nuclear protein 1 (NUPR1) or decreased levels of insulin receptor (INSR) characterize resistant cells. The secretion of non-VEGF pro-angiogenic factors, such as PDGF-BB, IL-1β, MMP-9, Gro-α, IL-8, IL-6, and CCL-2, can lead to resistance to cabozantinib. The reactivation of pathways previously targeted by lenvatinib or the activation of alternative pathways, such as EGFR-PAK2-ERK pathway, underlie the development of resistance to lenvatinib. Exploring resistance mechanism that arise during first-line therapy can lead to the development of treatment strategy able to overcome them in order to improve duration of response and patients outcomes.
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Affiliation(s)
- Matteo Santoni
- Medical Oncology Unit, Macerata Hospital, Macerata, Italy
| | - Veronica Mollica
- Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Alessandro Rizzo
- S.S.D. C.O.r.O. Bed Management Presa in Carico, TDM, IRCCS Istituto Tumori "Giovanni Paolo II", Bari, Italy
| | - Francesco Massari
- Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy.
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Wang Y, Liu Z, Huang W, Mao S, Zhang X, Chen L, Fang W, Hu P, Hong X, Du Y, Xu H. Development of a nomogram model for early prediction of refractory convulsive status epilepticus. Epilepsy Behav 2025; 163:110235. [PMID: 39742651 DOI: 10.1016/j.yebeh.2024.110235] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Revised: 12/11/2024] [Accepted: 12/22/2024] [Indexed: 01/04/2025]
Abstract
INTRODUCTION We aim to identify risk factors that predict refractory convulsive status epilepticus (RCSE) and to develop a model for early recognition of patients at high risk for RCSE. METHODS This study involved 200 patients diagnosed with convulsive status epilepticus (CSE), of whom 73 were RCSE and 127 were non-RCSE. Variables included demographic information, lifestyle factors, medical history, comorbidities, clinical symptoms, neuroimaging characteristics, laboratory tests, and nutritional scores. A predictive model was developed through multivariable logistic regression analysis. The model's predictive performance and clinical utility were evaluated using various metrics, including the area under the receiver operating characteristic (AUROC) curve, GiViTI calibration belt, and decision curve analysis (DCA). Additionally, we performed internal five-fold cross-validation for this model. RESULTS We developed a nomogram model with six predictors: age ≤ 40 years, prior history of epilepsy, presence of epileptic foci, duration of CSE > 30 min, c-reactive protein > 6 mg/L, and nutritional risk screening ≥ 3 points. Our model has a high AUROC (0.838) and good consistency (P = 0.999). In DCA, the curve of our model exhibits a positive net benefit across the entire range of threshold probabilities. Moreover, our model achieved an accuracy of 0.778 and a Kappa value of 0.519 in the five-fold cross-validation. CONCLUSION We developed an objective, simple and accessible model to assess the risk of RCSE. This model shows promise as a valuable tool for evaluating the individual risk of RCSE.
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Affiliation(s)
- Ying Wang
- Department of Neurology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, PR China
| | - Zhipeng Liu
- Department of Neurology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, PR China
| | - Wenting Huang
- Department of Neurology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, PR China
| | - Shumin Mao
- Department of Neurology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, PR China
| | - Xu Zhang
- Department of Neurology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, PR China
| | - Lekai Chen
- Department of Neurology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, PR China
| | - Wenqiang Fang
- Department of Neurology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, PR China
| | - Pinglang Hu
- Department of Neurology Nursing Unit 361 Ward, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, PR China
| | - Xianchai Hong
- Department of Neurology Nursing Unit 362 Ward, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, PR China
| | - Yanru Du
- Department of Neurology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, PR China.
| | - Huiqin Xu
- Department of Neurology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, PR China; Key Laboratory of Alzheimer's Disease of Zhejiang Province, Institute of Aging, Wenzhou Medical University, Wenzhou, Zhejiang Province, PR China.
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Martin-Quesada AI, Hennessy MA, Gutiérrez AC. Charting cancer's course: revealing the role of diet, exercise, and the microbiome in cancer evolution and immunotherapy response. Clin Transl Oncol 2025; 27:473-485. [PMID: 39095683 PMCID: PMC11782318 DOI: 10.1007/s12094-024-03595-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Accepted: 07/03/2024] [Indexed: 08/04/2024]
Abstract
A variety of pathophysiological mechanisms exist by which physical exercise, nutrition, and the microbiome can impact the development of cancer and the response of tumor cells to systemic anti-cancer therapy. Physical exercise positively impacts the different stages of oncological disease and may improve overall survival and quality of life, reduce treatment-associated toxicity, and improve response to immunotherapy. Nutrition impacts quality of life, and novel nutritional regimens and their role in cancer treatment and outcomes are under active investigation. Finally, the microbiome may act as a predictor of response and resistance to immunotherapy. This comprehensive review delves into the interplay between these elements and their impact on oncological outcomes, emphasizing their role in modulating the immune system and enhancing the response to immunotherapy.The data that support the findings of this study are openly available and referenced in the bibliography section.
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Affiliation(s)
- Ana Isabel Martin-Quesada
- Cell Therapy and Early Drug Development Unit, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
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Takahashi M, Aoyama A, Hamaji M, Sozu T, Kobayashi M, Nakagawa T, Ishikawa M, Miyahara R, Huang CL, Fujinaga T, Sakai H, Katakura H, Sonobe M, Okumura N, Kayawake H, Menju T, Miyamoto E, Miyata R, Okada H, Kono T, Sumitomo R, Date N, Fukada T, Matsumoto A, Sakaguchi Y, Date H. Clinical significance of the preoperative prognostic nutritional index in patients with resectable non-small cell lung cancer: a multicenter study. Surg Today 2025:10.1007/s00595-024-02987-8. [PMID: 39815110 DOI: 10.1007/s00595-024-02987-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Accepted: 11/05/2024] [Indexed: 01/18/2025]
Abstract
PURPOSE To validate the clinical impacts of the prognostic nutritional index (PNI), an immune-nutritional blood marker, in patients with resectable non-small cell lung cancer (NSCLC) using multicenter cohort data. METHODS The subjects of this retrospective multicenter study, involving 11 hospitals, were patients who underwent curative lung resection for pathological stage IA-IIIA NSCLC. We analyzed the relationship between the preoperative PNI and postoperative outcomes. Patients were divided into a high PNI group and a low PNI group (cutoff: 45). We also performed exact matching and three propensity score-based methods to validate the results. RESULTS Among the total 2,770 patients, 2,272 (82.0%) had a high PNI (>45) and 498 (18.0%) had a low PNI (≤45). A low preoperative PNI was a predictor of increased overall postoperative complications (relative risk 1.49; 95% confidence interval (CI) 1.31-1.69) and an independent adverse prognostic factor for overall survival (hazard ratio 1.77; 95% CI 1.45-2.17) and recurrence-free survival (1.34; 95% CI 1.14-1.59). All the methods we used (whole cohort, exact matching, and three propensity score methods) showed consistent results. CONCLUSIONS The findings of this multicenter study suggest that immune-nutritional assessment using the PNI will provide useful prognostic information for patients with resectable NSCLC.
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Affiliation(s)
- Mamoru Takahashi
- Department of Thoracic Surgery, Kyoto Katsura Hospital, 17 Yamada Hirao, Kyoto, 615-8256, Japan.
- Department of Thoracic Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
| | - Akihiro Aoyama
- Department of Thoracic Surgery, Kyoto Katsura Hospital, 17 Yamada Hirao, Kyoto, 615-8256, Japan
| | - Masatsugu Hamaji
- Department of Thoracic Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Takashi Sozu
- Department of Information and Computer Technology, Faculty of Engineering, Tokyo University of Science, Tokyo, Japan
| | - Masashi Kobayashi
- Department of Thoracic Surgery, Kurashiki Central Hospital, Kurashiki, Japan
| | - Tatsuo Nakagawa
- Department of Thoracic Surgery, Tenri Hospital, Tenri, Japan
| | - Masashi Ishikawa
- Department of Thoracic Surgery, Japanese Red Cross Wakayama Medical Center, Wakayama, Japan
| | - Ryo Miyahara
- Department of Thoracic Surgery, Kyoto City Hospital, Kyoto, Japan
| | | | - Takuji Fujinaga
- Department of Thoracic Surgery, Nagara Medical Center, Gifu, Japan
| | - Hiroaki Sakai
- Department of Thoracic Surgery, Amagasaki General Medical Center, Amagasaki, Japan
| | | | - Makoto Sonobe
- Department of Thoracic Surgery, Osaka Red Cross Hospital, Osaka, Japan
| | - Norihito Okumura
- Department of Thoracic Surgery, Kurashiki Central Hospital, Kurashiki, Japan
| | - Hidenao Kayawake
- Department of Thoracic Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Toshi Menju
- Department of Thoracic Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Ei Miyamoto
- Department of Thoracic Surgery, Tenri Hospital, Tenri, Japan
| | - Ryo Miyata
- Department of Thoracic Surgery, Japanese Red Cross Wakayama Medical Center, Wakayama, Japan
| | - Harutaro Okada
- Department of Thoracic Surgery, Kyoto Katsura Hospital, 17 Yamada Hirao, Kyoto, 615-8256, Japan
| | - Tomoya Kono
- Department of Thoracic Surgery, Kyoto City Hospital, Kyoto, Japan
| | - Ryota Sumitomo
- Department of Thoracic Surgery, Kitano Hospital, Osaka, Japan
| | - Naoki Date
- Department of Thoracic Surgery, Nagara Medical Center, Gifu, Japan
| | - Takehisa Fukada
- Department of Thoracic Surgery, Amagasaki General Medical Center, Amagasaki, Japan
| | - Akira Matsumoto
- Department of Thoracic Surgery, Otsu Red Cross Hospital, Otsu, Japan
| | - Yasuto Sakaguchi
- Department of Thoracic Surgery, Osaka Red Cross Hospital, Osaka, Japan
| | - Hiroshi Date
- Department of Thoracic Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan
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Yang SQ, Zou RQ, Dai YS, Hu HJ, Li FY. Prognostic evaluation in gallbladder carcinoma: Introducing a composite risk model integrating nutritional and immune markers. BIOMOLECULES & BIOMEDICINE 2025; 25:425-435. [PMID: 39067064 PMCID: PMC11734823 DOI: 10.17305/bb.2024.10673] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/26/2024] [Revised: 06/03/2024] [Accepted: 06/03/2024] [Indexed: 07/30/2024]
Abstract
The importance of evaluating the nutritional status and immune condition prior to surgery has gained significant attention in predicting the prognosis of cancer patients in recent years. The objective of this study is to establish a risk model for predicting the prognosis of gallbladder carcinoma (GBC) patients. Data from GBC patients who underwent radical resection at West China Hospital of Sichuan University (China) from 2014 to 2021 were retrospectively collected. A novel risk model was created by incorporating the prognostic nutritional index and glucose-to-lymphocyte ratio, and each patient was assigned a risk score. The patients were then divided into low- and high-risk cohorts, and comparisons were made between the two groups in terms of clinicopathological features and prognosis. Propensity score matching was conducted to reduce potential bias. A total of 300 GBC patients receiving radical surgery were identified and included in this study. Patients in the high-risk group were older, had higher levels of serum carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), and cancer antigen 19-9 (CA19-9), were more likely to experience postoperative complications, and had more aggressive tumor characteristics, such as poor differentiation, lymph node metastasis, and advanced tumor stage. They also had lower overall survival (OS) rates (5-year OS rate: 11.2% vs. 37.4%) and disease-free survival (DFS) rates (5-year DFS rate: 5.1% vs. 18.2%). After propensity score matching, the high-risk population still experienced poorer prognosis (5-year OS rate: 12.7% vs 20.5%; 5-year DFS rate: 3.2% vs 8.2%). The risk model combining prognostic nutritional index and glucose-to-lymphocyte ratio can serve as a standalone predictor for the prognosis and assist in optimizing the treatment approach for GBC patients.
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Affiliation(s)
- Si-qi Yang
- Division of Biliary Tract Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Rui-qi Zou
- Division of Biliary Tract Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Yu-shi Dai
- Division of Biliary Tract Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Hai-jie Hu
- Division of Biliary Tract Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Fu-yu Li
- Division of Biliary Tract Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
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Ghelardi F, Fucà G, Cavalli C, Shitara K, Cohen R, Ambrosini M, Maron SB, Cerantola R, Nasca V, Liberti GD, Zambelli L, Palazzo M, Salati M, Aoki Y, Kawazoe A, Cowzer D, Lonardi S, André T, Randon G, Pietrantonio F. The Prognostic Nutritional Index in patients with microsatellite instability-high metastatic gastric or gastroesophageal cancers receiving immune checkpoint inhibitors. Dig Liver Dis 2025; 57:23-29. [PMID: 38772790 DOI: 10.1016/j.dld.2024.05.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2024] [Revised: 04/22/2024] [Accepted: 05/06/2024] [Indexed: 05/23/2024]
Abstract
BACKGROUND Microsatellite instability high (MSI-H) and/or mismatch repair deficient (dMMR) status is the strongest predictive factor for immune checkpoint inhibitors (ICIs) benefit in patients with metastatic gastroesophageal cancer (mGC). Primary resistance to ICIs is a relevant issue, but prognostic and predictive factors are lacking. MATERIALS AND METHODS In this multinational, retrospective cohort of patients with MSI-H/dMMR mGC treated with ICIs without chemotherapy we collected baseline laboratory values to establish the prognostic nutritional index (PNI). We evaluated the association between baseline PNI with the activity and efficacy of ICIs. RESULTS At a median follow-up of 31.6 months, median progression-free survival (PFS) and 2-year PFS rate were not reached and 73.6 % in the PNI-high subgroup versus 6.3 months and 38.3 % in the PNI-low one (HR 0.32, 95 % CI: 0.16-0.61, p < .001). Median overall survival (OS) and 2-year OS rate were not reached and 81.9 % in the PNI-high subgroup versus 24.4 months and 50.5 % in the PNI-low one (HR 0.26, 95 % CI: 0.12-0.56, p < .001). In multivariable models, high PNI was associated with longer PFS and OS (HR 0.30, 95 % CI: 0.15-0.61, p <0.001 and 0.37, 95 % CI: 0.15-0.91, p = .031). CONCLUSIONS High PNI is associated with longer PFS and OS, in patients with MSI-H mGC receiving ICIs. Patients with low baseline PNI may benefit from intensive therapeutic approaches.
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Affiliation(s)
- Filippo Ghelardi
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
| | - Giovanni Fucà
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
| | - Chiara Cavalli
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
| | - Kohei Shitara
- Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, Japan
| | - Romain Cohen
- Sorbonne Université, INSERM, Unité Mixte de Recherche Scientifique 938 and SIRIC CURAMUS, Centre de Recherche Saint-Antoine, Equipe Instabilité des Microsatellites et Cancer, Equipe labellisée par la Ligue Nationale contre le Cancer, Paris, France
| | - Margherita Ambrosini
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
| | - Steven B Maron
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA
| | - Riccardo Cerantola
- Medical Oncology 1, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy
| | - Vincenzo Nasca
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
| | - Giorgia Di Liberti
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
| | - Luca Zambelli
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
| | - Michele Palazzo
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
| | - Massimiliano Salati
- Division of Oncology, Department of Oncology and Hematology, University Hospital of Modena, Modena, Italy; PhD Program Clinical and Experimental Medicine, University of Modena and Reggio Emilia, Modena, Italy
| | - Yu Aoki
- Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, Japan
| | - Akihito Kawazoe
- Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, Japan
| | - Darren Cowzer
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA
| | - Sara Lonardi
- Medical Oncology 3, Istituto Oncologico Veneto IOV-IRCCS, Padova, Italy
| | - Thierry André
- Sorbonne Université, INSERM, Unité Mixte de Recherche Scientifique 938 and SIRIC CURAMUS, Centre de Recherche Saint-Antoine, Equipe Instabilité des Microsatellites et Cancer, Equipe labellisée par la Ligue Nationale contre le Cancer, Paris, France
| | - Giovanni Randon
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
| | - Filippo Pietrantonio
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
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Alkan Şen G, Şentürk Öztaş N, Değerli E, Guliyev M, Turna H, Özgüroğlu M. Effect of body mass index on immune checkpoint inhibitor efficacy in patients with advanced cancer. TUMORI JOURNAL 2024; 110:437-442. [PMID: 39506383 DOI: 10.1177/03008916241291989] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2024]
Abstract
BACKGROUND The need for predictive factors regarding the response to immune checkpoint inhibitors (ICIs) is increasing. Recent research indicates that an enhanced response to ICIs is associated with a higher body mass index (BMI). This study aims to evaluate the relationship between response to ICIs and BMI in solid tumors. METHODS We retrospectively analyzed patients with advanced cancer treated with ICIs at one academic center. We compared the treatment responses of patients classified as underweight/normal weight (BMI <25) and overweight/obese (BMI ⩾ 25) according to their BMI at the initiation of ICI treatment. After excluding underweight patients, we also compared the progression-free survival (PFS) and overall survival (OS) of normal-weight, overweight, and obese patients. RESULTS Overall, 113 patients were evaluated. Forty-seven (41.6%) patients had BMI <25 and 66 (58.4%) patients had a BMI ⩾ 25. In underweight/normal patients, median PFS was 7.7 months (95% CI: 4.7-10.6) while it was 8.0 months (95% CI: 4.1-11.9) in overweight/obese patients (HR 1.16, 95% CI: (0.76-1.75), p=0.477). In underweight/normal patients, the median OS was 21.7 months (95% CI: 11.6-31.7) compared to 18.7 months (95% CI: 12.7-24.6) in overweight/obese patients (HR 1.06, 95% CI: (0.69-1.64), p=0.774). The objective response rate (ORR) was 38.3% in underweight/normal patients and 34.8% in overweight/obese patients (p = 0.707). After excluding underweight patients, there were also no significant differences in PFS (p = 0.914), OS (p = 0.642), and ORR (p = 0.909) between patients of normal weight, overweight, and obesity. CONCLUSION Our research found no correlation between BMI and response to ICIs. Additional prospective studies are necessary to assess the effect of BMI on the response to ICIs.
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Affiliation(s)
- Gülin Alkan Şen
- Division of Medical Oncology, Department of Internal Medicine, Cerrahpaşa Faculty of Medicine, İstanbul University-Cerrahpaşa, İstanbul, Turkey
| | - Nihan Şentürk Öztaş
- Division of Medical Oncology, Department of Internal Medicine, Cerrahpaşa Faculty of Medicine, İstanbul University-Cerrahpaşa, İstanbul, Turkey
| | - Ezgi Değerli
- Division of Medical Oncology, Department of Internal Medicine, Cerrahpaşa Faculty of Medicine, İstanbul University-Cerrahpaşa, İstanbul, Turkey
| | - Murad Guliyev
- Division of Medical Oncology, Department of Internal Medicine, Cerrahpaşa Faculty of Medicine, İstanbul University-Cerrahpaşa, İstanbul, Turkey
| | - Hande Turna
- Division of Medical Oncology, Department of Internal Medicine, Cerrahpaşa Faculty of Medicine, İstanbul University-Cerrahpaşa, İstanbul, Turkey
| | - Mustafa Özgüroğlu
- Division of Medical Oncology, Department of Internal Medicine, Cerrahpaşa Faculty of Medicine, İstanbul University-Cerrahpaşa, İstanbul, Turkey
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10
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Yu Y, Ning K, Liu X, Luo G, Liang Y, Hong L, Jiao Z, Wu T, Yang Z, Jiang M, Chen W, Yang A. Effectiveness of prognostic nutritional index in predicting overall survival and evaluating immunotherapy response in anaplastic thyroid carcinoma. Endocrine 2024; 86:246-254. [PMID: 38658474 DOI: 10.1007/s12020-024-03826-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2024] [Accepted: 04/07/2024] [Indexed: 04/26/2024]
Abstract
BACKGROUND The prognostic value of nutritional status in anaplastic thyroid carcinoma (ATC) remains unclear. The Prognostic Nutritional Index (PNI) is a reliable indicator of overall nutritional and immune status, and it has emerged as a significant prognostic factor in various malignancies. This study aimed to explore the utility of PNI in ATC. METHODS We systematically reviewed ATC patients in our institute from January 2000 to June 2023 and categorized them into high and low PNI groups based on the median PNI value. Kaplan-Meier analysis and Cox regression were employed to assess the impact of PNI on overall survival, while ROC curve analysis evaluated the predictive value of PNI. Mimics software was used for three-dimensional reconstruction of pre- and post-immunotherapy tumor volumes, enabling the assessment of treatment response. RESULTS A total of 77 ATC patients were included in this study. Low baseline PNI was associated with significantly shorter overall survival (1-year survival rate: 5.26% vs 30.77%; median survival time: 5.30 months vs 8.87 months). The 1-year, 2-year, and 3-year AUC values for PNI were 0.82, 0.79, and 0.77, respectively. In the multivariate analysis, both PNI and tumor size emerged as independent prognostic factors for patient overall survival. Among ATC patients receiving 2-3 cycles of immunotherapy, an increase in post-treatment PNI levels was positively correlated with a reduction in tumor volume. CONCLUSION PNI is an independent predictor of overall survival and holds the potential to serve as a valuable indicator for assessing and predicting immunotherapy efficacy in ATC patients.
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Affiliation(s)
- Yongchao Yu
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China
- Department of Head and Neck Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Kang Ning
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China
- Department of Head and Neck Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Xinyu Liu
- Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
| | - Guangfeng Luo
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China
- Department of Head and Neck Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Yarong Liang
- Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
| | - Lexuan Hong
- Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Zan Jiao
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China
- Department of Head and Neck Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Tong Wu
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China
- Department of Head and Neck Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Zhongyuan Yang
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China
- Department of Head and Neck Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Mingjie Jiang
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.
- Department of Head and Neck Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China.
| | - Weichao Chen
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.
- Department of Head and Neck Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China.
| | - Ankui Yang
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.
- Department of Head and Neck Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China.
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11
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Endo S, Imai H, Shiono A, Hashimoto K, Miura Y, Okazaki S, Abe T, Mouri A, Kaira K, Masubuchi K, Masubuchi T, Kobayashi K, Minato K, Kato S, Kagamu H. The Glasgow Prognostic Score as a Predictor of Survival after Chemoradiotherapy for Limited-Disease Small Cell Lung Cancer. Oncology 2024; 103:83-93. [PMID: 39102792 DOI: 10.1159/000540651] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2024] [Accepted: 07/26/2024] [Indexed: 08/07/2024]
Abstract
INTRODUCTION Established biomarkers for predicting chemoradiotherapy efficacy for limited-disease small cell lung cancer (LD-SCLC) are lacking. The inflammation-based Glasgow Prognostic Score (GPS), comprising serum C-reactive protein (CRP) and albumin levels, can predict survival in advanced cancer. This study investigated whether metabolic and inflammatory markers, including the GPS, can predict the efficacy of chemoradiotherapy in patients with LD-SCLC. METHODS We retrospectively analyzed 124 patients who underwent chemoradiotherapy for LD-SCLC at two institutions between April 2007 and June 2021, and assessed the prognostic significance of various metabolic and inflammatory markers. The GPS was calculated using the CRP and albumin concentrations, and categorized as follows: 0, CRP <1.0 mg/dL and albumin ≥3.5 mg/dL; 1, elevated CRP or decreased albumin; and 2, CRP ≥1.0 mg/dL and albumin<3.5 mg/dL. Differences in progression-free survival (PFS) and overall survival (OS) were examined using Kaplan-Meier curves and Cox proportional-hazard models. RESULTS The overall response rate was 95.1% (95% confidence interval [CI]: 89.6-97.9%). The median PFS and OS from chemoradiotherapy initiation were 12.6 (95% CI: 9.9-15.4) and 29.0 (95% CI: 24.8-45.5) months, respectively. The GPS demonstrated independent predictive ability for the effectiveness of chemoradiotherapy, wherein favorable scores (GPS 0-1) were significantly correlated with superior PFS and OS compared to unfavorable scores (GPS 2: PFS: 14.8 vs. 6.7 months, p = 0.0001; OS: 35.4 vs. 11.0 months, p < 0.0001). CONCLUSION This preliminary examination revealed that the GPS was significantly associated with PFS and OS in patients undergoing chemoradiotherapy for LD-SCLC, indicating its potential utility in assessing the therapeutic outcomes in LD-SCLC.
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Affiliation(s)
- Satoshi Endo
- Division of Respiratory Medicine, Gunma Prefectural Cancer Center, Ota, Japan
| | - Hisao Imai
- Division of Respiratory Medicine, Gunma Prefectural Cancer Center, Ota, Japan
- Department of Respiratory Medicine, International Medical Center, Saitama Medical University, Saitama, Japan
| | - Ayako Shiono
- Department of Respiratory Medicine, International Medical Center, Saitama Medical University, Saitama, Japan
| | - Kosuke Hashimoto
- Department of Respiratory Medicine, International Medical Center, Saitama Medical University, Saitama, Japan
| | - Yu Miura
- Department of Respiratory Medicine, International Medical Center, Saitama Medical University, Saitama, Japan
| | - Shohei Okazaki
- Division of Radiation Oncology, Gunma Prefectural Cancer Center, Ota, Japan
| | - Takanori Abe
- Department of Radiation Oncology, International Medical Center, Saitama Medical University, Saitama, Japan
| | - Atsuto Mouri
- Department of Respiratory Medicine, International Medical Center, Saitama Medical University, Saitama, Japan
| | - Kyoichi Kaira
- Department of Respiratory Medicine, International Medical Center, Saitama Medical University, Saitama, Japan
| | - Ken Masubuchi
- Division of Respiratory Medicine, Gunma Prefectural Cancer Center, Ota, Japan
| | - Takeshi Masubuchi
- Division of Respiratory Medicine, Gunma Prefectural Cancer Center, Ota, Japan
| | - Kunihiko Kobayashi
- Department of Respiratory Medicine, International Medical Center, Saitama Medical University, Saitama, Japan
| | - Koichi Minato
- Division of Respiratory Medicine, Gunma Prefectural Cancer Center, Ota, Japan
- Division of Health Evaluation and Promotion, SUBARU Health Insurance Society, Ota Memorial Hospital, Ota, Japan
| | - Shingo Kato
- Department of Radiation Oncology, International Medical Center, Saitama Medical University, Saitama, Japan
| | - Hiroshi Kagamu
- Department of Respiratory Medicine, International Medical Center, Saitama Medical University, Saitama, Japan
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12
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Horstman IM, Vinke PC, Suazo‐Zepeda E, Hiltermann TJN, Heuvelmans MA, Corpeleijn E, de Bock GH. The association of nutritional and inflammatory biomarkers with overall survival in patients with non-small-cell lung cancer treated with immune checkpoint inhibitors. Thorac Cancer 2024; 15:1764-1771. [PMID: 39030876 PMCID: PMC11320085 DOI: 10.1111/1759-7714.15401] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2024] [Revised: 06/18/2024] [Accepted: 06/21/2024] [Indexed: 07/22/2024] Open
Abstract
OBJECTIVES Pretreatment biomarkers are needed to identify patients with non-small-cell lung cancer (NSCLC) likely to have worse survival. This ensures that only patients with a real chance of benefit receive immune checkpoint inhibitor (ICI) treatment. In this study, we examined the associations of baseline nutritional and inflammatory biomarkers with overall survival in a real-world cohort of NSCLC patients who received ICIs. MATERIALS AND METHODS We used prospectively collected data from the OncoLifeS data biobank. The cohort included 500 advanced-stage NSCLC patients treated with ICIs from May 2015 to June 2021. Biomarkers were evaluated within 2 weeks before ICI treatment: neutrophil-to-lymphocyte ratio, C-reactive protein (CRP), Glasgow prognostic score, CRP/albumin ratio (CAR), prognostic nutritional index (PNI), and advanced lung cancer inflammation index. For each biomarker, low- and high-risk groups were defined using literature-based cut-offs. Adjusted hazard ratios (aHRs) and 95% confidence intervals (95% CIs) were estimated using adjusted survival analysis. RESULTS Most patients were male (60.8%), the mean baseline age was 65 ± 9 years, and 88% had stage IV disease. For each biomarker, low-risk patients had better overall survival (all, p < 0.001), with CAR and PNI showing the strongest associations. In multivariable analyses a combined CAR/PNI risk score had a stronger association with overall survival (aHR 3.09, 95% CI 2.36-4.06) than CAR alone (aHR 2.22, 95% CI 1.79-2.76) or PNI alone (aHR 2.09, 95% CI 1.66-2.61). CONCLUSION These results highlight the potential value of nutritional and inflammatory biomarkers, in particular CAR and PNI, in identifying NSCLC patients with highest mortality risk before starting ICI treatment.
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Affiliation(s)
- I. M. Horstman
- Department of Epidemiology, University Medical Center GroningenUniversity of GroningenGroningenthe Netherlands
| | - P. C. Vinke
- Department of Epidemiology, University Medical Center GroningenUniversity of GroningenGroningenthe Netherlands
| | - E. Suazo‐Zepeda
- Department of Epidemiology, University Medical Center GroningenUniversity of GroningenGroningenthe Netherlands
| | - T. J. N. Hiltermann
- Department of Pulmonology, University of GroningenUniversity Medical Center GroningenGroningenthe Netherlands
| | - M. A. Heuvelmans
- Department of Epidemiology, University Medical Center GroningenUniversity of GroningenGroningenthe Netherlands
| | - E. Corpeleijn
- Department of Epidemiology, University Medical Center GroningenUniversity of GroningenGroningenthe Netherlands
| | - G. H. de Bock
- Department of Epidemiology, University Medical Center GroningenUniversity of GroningenGroningenthe Netherlands
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13
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Kuang Z, Miao J, Zhang X. Serum albumin and derived neutrophil-to-lymphocyte ratio are potential predictive biomarkers for immune checkpoint inhibitors in small cell lung cancer. Front Immunol 2024; 15:1327449. [PMID: 38911864 PMCID: PMC11190784 DOI: 10.3389/fimmu.2024.1327449] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2023] [Accepted: 05/21/2024] [Indexed: 06/25/2024] Open
Abstract
Background Immune checkpoint inhibitors (ICIs) have reshaped the treatment landscape of small cell lung cancer (SCLC), but only a minority of patients benefit from this therapy. Therefore, it is critical to identify potential risk factors that could predict the efficacy of ICI treatment in SCLC patients and identify patient subgroups who may benefit the most from ICI therapy. Methods Our study included a total of 183 SCLC patients who had received at least one dose of ICI treatment. We utilized both logistic regression and Cox proportional hazard regression to evaluate whether various patient clinical factors and serum biomarkers could serve as predictors of patient response to treatment and overall survival (OS) during ICI therapy. Results Logistic regression showed that patients with a history of surgery (p=0.003, OR 9.06, 95% CI: (2.17, 37.9)) and no metastasis (p=0.008, OR 7.82, 95% CI: (1.73, 35.4)) exhibited a higher odds of response to ICI treatment. Cox regression analyses demonstrated that pretreatment blood albumin (p=0.003, HR 1.72, 95% CI: (1.21, 2.45)) and derived neutrophil to lymphocyte ratio (dNLR) (p=0.003, HR 1.71, 95% CI: (1.20-2.44)) were independent predictors for OS in SCLC patients. By establishing a pre-treatment prognostic scoring system based on baseline albumin and dNLR, we found that patients with high albumin and low dNLR exhibited a significantly better prognosis than those with low albumin and high dNLR in both the full (P<.0001, HR 0.33, 95% CI: 0.20-0.55) and the metastatic cohort (P<.0001, HR 0.28, 95% CI: 0.15-0.51). The better prognostic group also had younger age, higher BMI and lower systemic inflammatory biomarker values than the unfavorable group (P<.0001). Conclusion Our data reveals the significant role of metastasis status and treatment history in predicting the initial response of SCLC patients to ICI treatment. However, baseline serum albumin and dNLR provide a more precise prognostic prediction for patient OS. The scoring system based on albumin and dNLR enhances the ability to stratify patient prognosis and holds the potential to guide clinical decision-making for SCLC patients undergoing ICI therapy.
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Affiliation(s)
- Zhanpeng Kuang
- College of Public Health, The Ohio State University, Columbus, OH, United States
| | - Jessica Miao
- College of Arts and Sciences, The Ohio State University, Columbus, OH, United States
| | - Xiaoli Zhang
- Department of Biomedical Informatics, The Ohio State University, Columbus, OH, United States
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14
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Ni S, Liang Q, Jiang X, Ge Y, Jiang Y, Liu L. Prognostic models for immunotherapy in non-small cell lung cancer: A comprehensive review. Heliyon 2024; 10:e29840. [PMID: 38681577 PMCID: PMC11053285 DOI: 10.1016/j.heliyon.2024.e29840] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Revised: 04/11/2024] [Accepted: 04/16/2024] [Indexed: 05/01/2024] Open
Abstract
The introduction of immune checkpoint inhibitors (ICIs) has revolutionized the treatment of lung cancer. Given the limited clinical benefits of immunotherapy in patients with non-small cell lung cancer (NSCLC), various predictors have been shown to significantly influence prognosis. However, no single predictor is adequate to forecast patients' survival benefit. Therefore, it's imperative to develop a prognostic model that integrates multiple predictors. This model would be instrumental in identifying patients who might benefit from ICIs. Retrospective analysis and small case series have demonstrated the potential role of these models in prognostic prediction, though further prospective investigation is required to evaluate more rigorously their application in these contexts. This article presents and summarizes the latest research advancements on immunotherapy prognostic models for NSCLC from multiple omics perspectives and discuss emerging strategies being developed to enhance the domain.
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Affiliation(s)
- Siqi Ni
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
| | - Qi Liang
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
| | - Xingyu Jiang
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
| | - Yinping Ge
- The Friendship Hospital of Ili Kazakh Autonomous Prefecture Ili & Jiangsu Joint Institute of Health, Yining 835000, Xinjiang Uygur Autonomous Regio, China
| | - Yali Jiang
- The Friendship Hospital of Ili Kazakh Autonomous Prefecture Ili & Jiangsu Joint Institute of Health, Yining 835000, Xinjiang Uygur Autonomous Regio, China
| | - Lingxiang Liu
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
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15
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Raoul P, De Gaetano V, Sciaraffia G, Ormea G, Cintoni M, Pozzo C, Strippoli A, Gasbarrini A, Mele MC, Rinninella E. Gastric Cancer, Immunotherapy, and Nutrition: The Role of Microbiota. Pathogens 2024; 13:357. [PMID: 38787209 PMCID: PMC11124250 DOI: 10.3390/pathogens13050357] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2024] [Revised: 04/14/2024] [Accepted: 04/23/2024] [Indexed: 05/25/2024] Open
Abstract
Immune checkpoint inhibitors (ICI) have revolutionized the treatment of gastric cancer (GC), which still represents the third leading cause of cancer-related death in Western countries. However, ICI treatment outcomes vary between individuals and need to be optimized. Recent studies have shown that gut microbiota could represent a key influencer of immunotherapy responses. At the same time, the nutritional status and diet of GC patients are also predictive of immunotherapy treatment response and survival outcomes. The objective of this narrative review is to gather recent findings about the complex relationships between the oral, gastric, and gut bacterial communities, dietary factors/nutritional parameters, and immunotherapy responses. Perigastric/gut microbiota compositions/functions and their metabolites could be predictive of response to immunotherapy in GC patients and even overall survival. At the same time, the strong influence of diet on the composition of the microbiota could have consequences on immunotherapy responses through the impact of muscle mass in GC patients during immunotherapy. Future studies are needed to define more precisely the dietary factors, such as adequate daily intake of prebiotics, that could counteract the dysbiosis of the GC microbiota and the impaired nutritional status, improving the clinical outcomes of GC patients during immunotherapy.
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Affiliation(s)
- Pauline Raoul
- Clinical Nutrition Unit, Department of Medical and Abdominal Surgery and Endocrine-Metabolic Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy (M.C.); (M.C.M.)
| | - Valeria De Gaetano
- School of Specialization in Internal Medicine, Catholic University of the Sacred Heart, 00168 Rome, Italy; (V.D.G.); (G.S.)
| | - Gianmario Sciaraffia
- School of Specialization in Internal Medicine, Catholic University of the Sacred Heart, 00168 Rome, Italy; (V.D.G.); (G.S.)
| | - Ginevra Ormea
- Degree Course in Pharmacy, Catholic University of the Sacred Heart, 00168 Rome, Italy;
| | - Marco Cintoni
- Clinical Nutrition Unit, Department of Medical and Abdominal Surgery and Endocrine-Metabolic Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy (M.C.); (M.C.M.)
- Research and Training Center in Human Nutrition, Catholic University of the Sacred Heart, 00168 Rome, Italy;
| | - Carmelo Pozzo
- Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy; (C.P.); (A.S.)
| | - Antonia Strippoli
- Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy; (C.P.); (A.S.)
| | - Antonio Gasbarrini
- Research and Training Center in Human Nutrition, Catholic University of the Sacred Heart, 00168 Rome, Italy;
- Digestive Disease Center (CEMAD), Department of Medical and Abdominal Surgery and Endocrine-Metabolic Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Department of Translational Medicine and Surgery, Catholic University of the Sacred Heart, 00168 Rome, Italy
| | - Maria Cristina Mele
- Clinical Nutrition Unit, Department of Medical and Abdominal Surgery and Endocrine-Metabolic Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy (M.C.); (M.C.M.)
- Research and Training Center in Human Nutrition, Catholic University of the Sacred Heart, 00168 Rome, Italy;
- Department of Translational Medicine and Surgery, Catholic University of the Sacred Heart, 00168 Rome, Italy
| | - Emanuele Rinninella
- Clinical Nutrition Unit, Department of Medical and Abdominal Surgery and Endocrine-Metabolic Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy (M.C.); (M.C.M.)
- Research and Training Center in Human Nutrition, Catholic University of the Sacred Heart, 00168 Rome, Italy;
- Department of Translational Medicine and Surgery, Catholic University of the Sacred Heart, 00168 Rome, Italy
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16
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Zhang B, Chen J, Yu H, Li M, Cai M, Chen L. Prognostic Nutritional Index Predicts Efficacy and Immune-Related Adverse Events of First-Line Chemoimmunotherapy in Patients with Extensive-Stage Small-Cell Lung Cancer. J Inflamm Res 2024; 17:1777-1788. [PMID: 38523686 PMCID: PMC10959246 DOI: 10.2147/jir.s450804] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Accepted: 03/12/2024] [Indexed: 03/26/2024] Open
Abstract
Background Currently, there is a lack of well-established markers to predict the efficacy of chemoimmunotherapy in small-cell lung cancer (SCLC). Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), advanced lung cancer inflammation index (ALI) and prognostic nutritional index (PNI) are associated with prognosis in several tumors, whereas their predictive role in SCLC remains unclear. Methods A retrospective study was conducted at Sun Yat-sen University Cancer Center, involving extensive-stage SCLC (ES-SCLC) patients who received first-line chemoimmunotherapy between January 2020 and December 2021. Peripheral blood biomarkers were extracted from medical records and their correlation with prognosis and immune-related adverse events (IRAEs) was analyzed. Results A total of 114 patients were included. Patients with a low PLR, high ALI and high PNI had prolonged progression-free survival (PFS) compared to those with a high PLR, low ALI and low PNI. Patients with a low NLR, low PLR, high ALI and high PNI had prolonged overall survival (OS) compared to those with a high NLR, high PLR, low ALI and low PNI. Cox regression model showed that PNI was an independent risk factor for both PFS and OS. ROC curve showed that PNI outperforms NLR, PLR and ALI in predicting both PFS and OS. The PNI-based nomogram demonstrated strong predictive capability for both PFS and OS. In addition, there was a significant correlation between PNI and IRAEs. Conclusion A high baseline PNI might be associated with improved prognosis and the occurrence of IRAEs in ES-SCLC patients treated with first-line chemoimmunotherapy.
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Affiliation(s)
- Baishen Zhang
- Sun Yat-Sen University Cancer Center; State Key Laboratory of Oncology in South China; Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, People’s Republic of China
| | - Jing Chen
- Department of Medical Oncology, Sun Yat-Sen University Cancer Center; State Key Laboratory of Oncology in South China; Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, People’s Republic of China
| | - Hui Yu
- Department of Medical Oncology, Sun Yat-Sen University Cancer Center; State Key Laboratory of Oncology in South China; Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, People’s Republic of China
| | - Meichen Li
- Department of Medical Oncology, Sun Yat-Sen University Cancer Center; State Key Laboratory of Oncology in South China; Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, People’s Republic of China
| | - Muyan Cai
- Department of Pathology, Sun Yat-Sen University Cancer Center; State Key Laboratory of Oncology in South China; Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, People’s Republic of China
| | - Likun Chen
- Department of Medical Oncology, Sun Yat-Sen University Cancer Center; State Key Laboratory of Oncology in South China; Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, People’s Republic of China
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Raynes G, Stares M, Low S, Haron D, Sarwar H, Abhi D, Barrie C, Laird B, Phillips I, MacKean M. Immune-Related Adverse Events, Biomarkers of Systemic Inflammation, and Survival Outcomes in Patients Receiving Pembrolizumab for Non-Small-Cell Lung Cancer. Cancers (Basel) 2023; 15:5502. [PMID: 38067207 PMCID: PMC10705211 DOI: 10.3390/cancers15235502] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2023] [Revised: 11/08/2023] [Accepted: 11/08/2023] [Indexed: 11/05/2024] Open
Abstract
BACKGROUND Pembrolizumab monotherapy for non-small-cell lung cancer (NSCLC) expressing PD-L1 ≥ 50% doubles five-year survival rates compared to chemotherapy. However, immune-related adverse events (irAEs) can cause severe, long-term toxicity necessitating high-dose steroids and/or treatment cessation. Interestingly, patients experiencing irAEs demonstrate better survival outcomes. Biomarkers of systemic inflammation, including the Scottish Inflammatory Prognostic Score (SIPS), also predict survival in this patient group. This study examines the relationship between inflammatory status, irAEs, and survival outcomes in NSCLC. METHODS A retrospective analysis was conducted on patients with NSCLC expressing PD-L1 ≥ 50% receiving first-line pembrolizumab monotherapy at a large cancer centre in Scotland. Regression analyses were conducted to examine the relationship between SIPS, irAEs, and survival. RESULTS 83/262 eligible patients (32%) experienced an irAE. Dermatological, endocrine, gastrointestinal, and hepatic, but not pulmonary, irAEs were associated with prolonged PFS and OS (p <= 0.011). Mild irAEs were associated with better PFS and OS in all patients, including on time-dependent analyses (HR0.61 [95% CI 0.41-0.90], p = 0.014 and HR0.41 [95% CI 0.26-0.63], p < 0.001, respectively). SIPS predicted PFS (HR 1.60 [95% CI 1.34-1.90], p < 0.001) and OS (HR 1.69 [95% CI 1.41-2.02], p < 0.001). SIPS predicted the occurrence of any irAE in all patients (p = 0.011), but not on 24-week landmark analyses (p = 0.174). The occurrence of irAEs predicted favourable outcomes regardless of the baseline inflammatory status (p = 0.015). CONCLUSION The occurrence of certain irAEs is associated with a survival benefit in patients with NSCLC expressing PD-L1 ≥ 50% receiving pembrolizumab. We find that the association between low levels of systemic inflammation and the risk of irAEs is confounded by their independent prognostic value.
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Affiliation(s)
- George Raynes
- Edinburgh Cancer Centre, NHS Lothian, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UK
| | - Mark Stares
- Edinburgh Cancer Centre, NHS Lothian, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UK
- Cancer Research UK Scotland Centre, Institute of Genetics and Cancer, Western General Hospital, University of Edinburgh, Crewe Road South, Edinburgh EH4 2XR, UK
| | - Samantha Low
- Edinburgh Cancer Centre, NHS Lothian, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UK
| | - Dhania Haron
- Edinburgh Cancer Centre, NHS Lothian, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UK
| | - Hussain Sarwar
- Edinburgh Cancer Centre, NHS Lothian, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UK
| | - Dhruv Abhi
- Edinburgh Cancer Centre, NHS Lothian, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UK
| | - Colin Barrie
- Edinburgh Cancer Centre, NHS Lothian, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UK
| | - Barry Laird
- Cancer Research UK Scotland Centre, Institute of Genetics and Cancer, Western General Hospital, University of Edinburgh, Crewe Road South, Edinburgh EH4 2XR, UK
| | | | - Iain Phillips
- Edinburgh Cancer Centre, NHS Lothian, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UK
- Cancer Research UK Scotland Centre, Institute of Genetics and Cancer, Western General Hospital, University of Edinburgh, Crewe Road South, Edinburgh EH4 2XR, UK
| | - Melanie MacKean
- Edinburgh Cancer Centre, NHS Lothian, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UK
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Nishihara-Kato F, Imai H, Tsuda T, Wasamoto S, Nagai Y, Kishikawa T, Miura Y, Ono A, Yamada Y, Masubuchi K, Osaki T, Nakagawa J, Umeda Y, Minemura H, Kozu Y, Taniguchi H, Ohta H, Kaira K, Kagamu H. Prognostic Potential of the Prognostic Nutritional Index in Non-Small Cell Lung Cancer Patients Receiving Pembrolizumab Combination Therapy with Carboplatin and Paclitaxel/Nab-Paclitaxel. Oncology 2023; 102:30-42. [PMID: 37598676 DOI: 10.1159/000533604] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Accepted: 07/12/2023] [Indexed: 08/22/2023]
Abstract
INTRODUCTION Pembrolizumab (Pemb) therapy in conjunction with carboplatin and paclitaxel (PTX)/nab-PTX has been efficacious in treating non-small cell lung cancer (NSCLC). However, the response predictors of this combination therapy (Pemb-combination) remain undetermined. We aimed to evaluate whether Glasgow prognostic score (GPS), neutrophil-to-lymphocyte ratio (NLR), body mass index (BMI), platelet-to-lymphocyte ratio (PLR), and prognostic nutritional index (PNI) are potential factors in prognosticating the response to Pemb-combination therapy in advanced NSCLC patients. METHODS We retrospectively recruited 144 NSCLC patients receiving first-line treatment with Pemb-combination therapy from 13 institutions between December 1, 2018, and December 31, 2020. GPS, NLR, BMI, PLR, and PNI were assessed for their efficacy as prognostic indicators. Cox proportional hazard models and the Kaplan-Meier method were used to compare the progression-free survival (PFS) and overall survival (OS) of the patients. RESULTS The treatment exhibited a response rate of 63.1% (95% confidence interval [CI]: 55.0-70.6%). Following Pemb-combination administration, the median PFS and OS were 7.3 (95% CI: 5.3-9.4) and 16.5 (95% CI: 13.9-22.1) months, respectively. Contrary to PNI, NLR, GPS, BMI, and PLR did not display substantially different PFS in univariate analysis. However, multivariate analysis did not identify PNI as an independent prognostic factor for PFS. Furthermore, univariate analysis revealed that GPS, BMI, and PLR exhibited similar values for OS but not NLR and PNI. Patients with PNI ≥45 were predicted to have better OS than those with PNI <45 (OS: 23.4 and 13.9 months, respectively, p = 0.0028). Multivariate analysis did not establish NLR as an independent prognostic factor for OS. CONCLUSION The PNI evidently predicted OS in NSCLC patients treated with Pemb-combination as first-line therapy, thereby validating its efficiency as a prognostic indicator of NSCLC.
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Affiliation(s)
- Fuyumi Nishihara-Kato
- Department of Respiratory Medicine, Comprehensive Cancer Center, International Medical Center, Saitama Medical University, Saitama, Japan
| | - Hisao Imai
- Department of Respiratory Medicine, Comprehensive Cancer Center, International Medical Center, Saitama Medical University, Saitama, Japan
- Division of Respiratory Medicine, Gunma Prefectural Cancer Center, Ota, Japan
| | - Takeshi Tsuda
- Division of Respiratory Medicine, Toyama Prefectural Central Hospital, Toyama, Japan
| | - Satoshi Wasamoto
- Division of Respiratory Medicine, Saku Central Hospital Advanced Care Center, Saku, Japan
| | - Yoshiaki Nagai
- Department of Respiratory Medicine, Jichi Medical University, Saitama Medical Center, Saitama, Japan
| | | | - Yosuke Miura
- Division of Allergy and Respiratory Medicine, Integrative Center of Internal Medicine, Gunma University Hospital, Maebashi, Japan
| | - Akihiro Ono
- Division of Internal Medicine, Kiryu Kosei General Hospital, Kiryu, Japan
| | - Yutaka Yamada
- Division of Respiratory Medicine, Ibaraki Prefectural Central Hospital, Kasama, Japan
| | - Ken Masubuchi
- Division of Respiratory Medicine, Gunma Prefectural Cancer Center, Ota, Japan
| | - Takashi Osaki
- Division of Respiratory Medicine, National Hospital Organization Shibukawa Medical Center, Shibukawa, Japan
| | - Junichi Nakagawa
- Division of Respiratory Medicine, National Hospital Organization Takasaki General Medical Center, Takasaki, Japan
| | - Yukihiro Umeda
- Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Hiroyuki Minemura
- Department of Pulmonary Medicine, Fukushima Medical University, Fukushima, Japan
| | - Yuki Kozu
- Division of Respiratory Medicine, Saku Central Hospital Advanced Care Center, Saku, Japan
| | - Hirokazu Taniguchi
- Division of Respiratory Medicine, Toyama Prefectural Central Hospital, Toyama, Japan
| | - Hiromitsu Ohta
- Department of Respiratory Medicine, Jichi Medical University, Saitama Medical Center, Saitama, Japan
| | - Kyoichi Kaira
- Department of Respiratory Medicine, Comprehensive Cancer Center, International Medical Center, Saitama Medical University, Saitama, Japan
| | - Hiroshi Kagamu
- Department of Respiratory Medicine, Comprehensive Cancer Center, International Medical Center, Saitama Medical University, Saitama, Japan
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MacDonald M, Poei D, Leyba A, Diep R, Chennapan K, Leon C, Xia B, Nieva JJ, Hsu R. Real world prognostic utility of platelet lymphocyte ratio and nutritional status in first-line immunotherapy response in stage IV non-small cell lung cancer. Cancer Treat Res Commun 2023; 36:100752. [PMID: 37611343 PMCID: PMC11160511 DOI: 10.1016/j.ctarc.2023.100752] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2023] [Revised: 07/25/2023] [Accepted: 08/14/2023] [Indexed: 08/25/2023]
Abstract
BACKGROUND Elevated platelet lymphocyte ratio (PLR) and low body mass index (BMI) are associated with inferior survival in non-small cell lung cancer (NSCLC) patients receiving immunotherapy (IO). We evaluated real-world prognostic utility of PLR, BMI, and albumin level in stage IV NSCLC patients receiving first line (1L) IO. METHODS We identified 75 stage IV patients who received 1L IO therapy at USC Norris Comprehensive Cancer Center and Los Angeles General Medical Center from 2015 to 2022. The primary outcome was overall survival (OS) from time of IO with attention to pre-treatment BMI < 22, albumin < 3.5 g/dL, and PLR > 180. RESULTS Median age was 66.5 years with 49 (65.3%) males. 25 (33.3%) had BMI < 22. 45/75 (60%) had PLR > 180. Patients with BMI < 22 had inferior OS (13.1 months (m) vs. 37.4 m in BMI > 28, p-value = 0.042) along with patients with albumin<3.5 g/dL (OS: 2.8 m vs. 14.6 m, p-value = 0.0027), and patients with PLR>180 (OS: 8.7 m vs. 23.0 m, p = 0.028). Composite BMI < 22, PLR > 180 had the worst OS, p-value = 0.0331. Multivariate analysis controlling for age, smoking, gender, PD-L1 tumor proportion score (TPS), and histology (adenocarcinoma, squamous, adenosquamous, and large cell) showed that BMI (HR: 0.8726, 95% CI: 0.7892-0.954) and PLR > 180 (HR: 2.48, 95% CI: 1.076-6.055) were significant in OS mortality risk. CONCLUSION Patients with a composite of BMI < 22, albumin < 3.5 g/dL, and PLR > 180 had significantly worse OS. This highlights the importance of screening for poor nutritional status and high PLR to better inform stage IV NSCLC patients receiving IO therapy of their prognosis and supportive care. MICROABSTRACT We evaluated real-world prognostic utility of platelet lymphocyte ratio (PLR), body mass index (BMI), and albumin level in 75 Stage IV NSCLC patients receiving first line IO. Patients with a composite of BMI < 22, albumin < 3.5 g/dL, and PLR > 180 had significantly worse OS. This highlights the importance of screening for poor nutritional status and high PLR to better inform stage IV NSCLC patients of their prognosis and to emphasize supportive care needs.
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Affiliation(s)
- Madeline MacDonald
- Department of Internal Medicine, University of Southern California, Los Angeles, CA, United States
| | - Darin Poei
- Department of Internal Medicine, University of Southern California, Los Angeles, CA, United States
| | - Alexis Leyba
- Department of Internal Medicine, University of Southern California, Los Angeles, CA, United States
| | - Raymond Diep
- California University of Science and Medicine SOM, Colton, CA, United States
| | - Krithika Chennapan
- Department of Internal Medicine, University of Southern California, Los Angeles, CA, United States
| | - Christopher Leon
- Department of Surgery, University of Southern California, Los Angeles, CA, United States
| | - Bing Xia
- Department of Internal Medicine, Division of Medical Oncology, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, United States
| | - Jorge J Nieva
- Department of Internal Medicine, Division of Medical Oncology, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, United States
| | - Robert Hsu
- Department of Internal Medicine, Division of Medical Oncology, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, United States.
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Zhai WY, Duan FF, Lin YB, Lin YB, Zhao ZR, Wang JY, Rao BY, Zheng L, Long H. Pan-Immune-Inflammatory Value in Patients with Non-Small-Cell Lung Cancer Undergoing Neoadjuvant Immunochemotherapy. J Inflamm Res 2023; 16:3329-3339. [PMID: 37576157 PMCID: PMC10422963 DOI: 10.2147/jir.s418276] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2023] [Accepted: 08/01/2023] [Indexed: 08/15/2023] Open
Abstract
Background We aimed to investigate the predictive value of a systematic serum inflammation index, pan-immune-inflammatory value (PIV), in pathological complete response (pCR) of patients treated with neoadjuvant immunotherapy to further promote ideal patients' selection. Methods The clinicopathological and baseline laboratory information of 128 NSCLC patients receiving neoadjuvant immunochemotherapy between October 2019 and April 2022 were retrospectively reviewed. We performed least absolute shrinkage and selection operator (LASSO) algorithm to screen candidate serum biomarkers for predicting pCR, which further entered the multivariate logistic regression model to determine final biomarkers. Accordingly, a diagnostic model for predicting individual pCR was established. Kaplan-Meier method was utilized to estimate curves of disease-free survival (DFS), and the Log rank test was analyzed to compare DFS differences between patients with and without pCR. Results Patients with NSCLC heterogeneously responded to neoadjuvant immunotherapy, and those with pCR had a significant longer DFS than patients without pCR. Through LASSO and the multivariate logistic regression model, PIV was identified as a predictor for predicting pCR of patients. Subsequently, a diagnostic model integrating with PIV, differentiated degree and histological type was constructed to predict pCR, which presented a satisfactory predictive power (AUC, 0.736), significant agreement between actual and our nomogram-predicted pathological response. Conclusion Baseline PIV was an independent predictor of pCR for NSCLC patients receiving neoadjuvant immunochemotherapy. A significantly longer DFS was achieved in patients with pCR rather than those without pCR; thus, the PIV-based diagnostic model might serve as a practical tool to identify ideal patients for neoadjuvant immunotherapeutic guidance.
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Affiliation(s)
- Wen-Yu Zhai
- Department of Thoracic Surgery, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China
- Lung Cancer Research Center, Sun Yat-Sen University, Guangzhou, People’s Republic of China
| | - Fang-Fang Duan
- Department of Medical oncology, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China
| | - Yao-Bin Lin
- Department of Thoracic Surgery, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China
- Lung Cancer Research Center, Sun Yat-Sen University, Guangzhou, People’s Republic of China
| | - Yong-Bin Lin
- Department of Thoracic Surgery, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China
- Lung Cancer Research Center, Sun Yat-Sen University, Guangzhou, People’s Republic of China
| | - Ze-Rui Zhao
- Department of Thoracic Surgery, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China
- Lung Cancer Research Center, Sun Yat-Sen University, Guangzhou, People’s Republic of China
| | - Jun-Ye Wang
- Department of Thoracic Surgery, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China
- Lung Cancer Research Center, Sun Yat-Sen University, Guangzhou, People’s Republic of China
| | - Bing-Yu Rao
- Department of Thoracic Surgery, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China
- Lung Cancer Research Center, Sun Yat-Sen University, Guangzhou, People’s Republic of China
| | - Lie Zheng
- Medical Imaging Division, Department of Medical Imaging and Interventional Radiology, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China
| | - Hao Long
- Department of Thoracic Surgery, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China
- Lung Cancer Research Center, Sun Yat-Sen University, Guangzhou, People’s Republic of China
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21
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Hes C, Jagoe RT. Gut microbiome and nutrition-related predictors of response to immunotherapy in cancer: making sense of the puzzle. BJC REPORTS 2023; 1:5. [PMID: 39516566 PMCID: PMC11523987 DOI: 10.1038/s44276-023-00008-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Revised: 06/07/2023] [Accepted: 07/05/2023] [Indexed: 11/16/2024]
Abstract
The gut microbiome is emerging as an important predictor of response to immune checkpoint inhibitor (ICI) therapy for patients with cancer. However, several nutrition-related patient characteristics, which are themselves associated with changes in gut microbiome, are also prognostic markers for ICI treatment response and survival. Thus, increased abundance of Akkermansia muciniphila, Phascolarctobacterium, Bifidobacterium and Rothia in stool are consistently associated with better response to ICI treatment. A. muciniphila is also more abundant in stool in patients with higher muscle mass, and muscle mass is a strong positive prognostic marker in cancer, including after ICI treatment. This review explores the complex inter-relations between the gut microbiome, diet and patient nutritional status and the correlations with response to ICI treatment. Different multivariate approaches, including archetypal analysis, are discussed to help identify the combinations of features which may select patients most likely to respond to ICI treatment.
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Affiliation(s)
- Cecilia Hes
- Peter Brojde Lung Cancer Centre, Segal Cancer Center, Jewish General Hospital, Montreal, QC, H3T 1E2, Canada
- Division of Experimental Medicine, Faculty of Medicine and Health Sciences, McGill University, Montreal, QC, H4A 3J1, Canada
- Research Center of the Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, H2X 0A9, Canada
| | - R Thomas Jagoe
- Peter Brojde Lung Cancer Centre, Segal Cancer Center, Jewish General Hospital, Montreal, QC, H3T 1E2, Canada.
- Division of Experimental Medicine, Faculty of Medicine and Health Sciences, McGill University, Montreal, QC, H4A 3J1, Canada.
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22
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Yan X, Wang J, Mao J, Wang Y, Wang X, Yang M, Qiao H. Identification of prognostic nutritional index as a reliable prognostic indicator for advanced lung cancer patients receiving immune checkpoint inhibitors. Front Nutr 2023; 10:1213255. [PMID: 37575320 PMCID: PMC10416798 DOI: 10.3389/fnut.2023.1213255] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Accepted: 07/12/2023] [Indexed: 08/15/2023] Open
Abstract
Background Prognostic nutritional index (PNI) has been identified as a reliable prognostic factor for cancer adjuvant therapy. However, its prognostic value in lung cancer patients receiving immune checkpoint inhibitors (ICIs) remains inconclusive. Method A systematic literature review and meta-analysis was performed based on online databases before March 1th 2023. The correlation of PNI with overall survival (OS) or progression-free survival (PFS) was determined using the hazard ratios (HRs) coupled with 95% confidence intervals (CIs). Then, a retrospective cohort enrolling 123 ICI-treated lung cancer patients from two hospitals was utilized for validation and further investigation. Results A total of 14 studies enrolling 1,260 lung cancer patients were included in the meta-analysis. The high PNI level was significantly correlated with better OS (HR = 2.56, 95% CI = 1.86-3.54) and PFS (HR = 1.91, 95% CI = 1.53-2.40) of the lung cancer patients. The subgroup analysis confirmed the results except for the PFS in patients receiving anti-PD-1 therapy (HR = 1.51, 95% CI = 0.86-2.65). In the retrospective study, the high PNI level was identified as a favorable factor for OS and PFS not only in the whole cohort but also in the subgroups stratified by non-small cell lung cancer and small cell lung cancer. The high PNI was also correlated with better anti-cancer therapy response and performed better than body mass index and serum albumin level in OS prediction. Finally, we established a novel prognostic nomogram based on PNI and other clinical parameters. The nomogram was found to perform well in predicting the 1-year OS of ICI-treated lung cancer patients. Conclusion Both the meta-analysis and retrospective work demonstrate the PNI is a reliable prognostic factor for advanced lung cancer patients receiving ICI-based therapies. Our study further highlights the crucial role of nutrition assessment and intervention in cancer immunotherapy. Systematic review registration https://www.crd.york.ac.uk/prospero/, identifier: CRD42023424146.
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Affiliation(s)
- Xuebing Yan
- Department of Oncology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
| | - Jiaxin Wang
- Department of Oncology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
| | - Jingxian Mao
- Department of Oncology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
| | - Ying Wang
- Department of Oncology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
| | - Xiangjun Wang
- Department of Oncology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
| | - Mengxue Yang
- Department of Oncology, Hefei Cancer Hospital, Chinese Academy of Sciences, Hefei, China
| | - Hong Qiao
- Department of Oncology, Baoying Traditional Chinese Medicine Hospital, Yangzhou, China
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23
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Pizzutilo EG, Romanò R, Roazzi L, Agostara AG, Oresti S, Zeppellini A, Giannetta L, Cerea G, Signorelli D, Siena S, Sartore-Bianchi A. Immune Checkpoint Inhibitors and the Exposome: Host-Extrinsic Factors Determine Response, Survival, and Toxicity. Cancer Res 2023; 83:2283-2296. [PMID: 37205627 PMCID: PMC10345966 DOI: 10.1158/0008-5472.can-23-0161] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Revised: 03/24/2023] [Accepted: 05/15/2023] [Indexed: 05/21/2023]
Abstract
Cancer immunotherapy, largely represented by immune checkpoint inhibitors (ICI), has led to substantial changes in preclinical cancer research and clinical oncology practice over the past decade. However, the efficacy and toxicity profiles of ICIs remain highly variable among patients, with only a fraction achieving a significant benefit. New combination therapeutic strategies are being investigated, and the search for novel predictive biomarkers is ongoing, mainly focusing on tumor- and host-intrinsic components. Less attention has been directed to all the external, potentially modifiable factors that compose the exposome, including diet and lifestyle, infections, vaccinations, and concomitant medications, that could affect the immune system response and its activity against cancer cells. We hereby provide a review of the available clinical evidence elucidating the impact of host-extrinsic factors on ICI response and toxicity.
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Affiliation(s)
- Elio Gregory Pizzutilo
- Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy
- Università degli Studi di Milano, Department of Oncology and Hemato-Oncology, Milan, Italy
| | - Rebecca Romanò
- Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy
- Università degli Studi di Milano, Department of Oncology and Hemato-Oncology, Milan, Italy
| | - Laura Roazzi
- Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy
- Università degli Studi di Milano, Department of Oncology and Hemato-Oncology, Milan, Italy
| | - Alberto G. Agostara
- Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy
- Università degli Studi di Milano, Department of Oncology and Hemato-Oncology, Milan, Italy
| | - Sara Oresti
- Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy
- Università degli Studi di Milano, Department of Oncology and Hemato-Oncology, Milan, Italy
| | - Annalisa Zeppellini
- Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Laura Giannetta
- Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Giulio Cerea
- Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Diego Signorelli
- Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Salvatore Siena
- Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy
- Università degli Studi di Milano, Department of Oncology and Hemato-Oncology, Milan, Italy
| | - Andrea Sartore-Bianchi
- Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy
- Università degli Studi di Milano, Department of Oncology and Hemato-Oncology, Milan, Italy
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He Z, Zhang C, Ran M, Deng X, Wang Z, Liu Y, Li H, Lou J, Mi W, Cao J. The modified lymphocyte C-reactive protein score is a promising indicator for predicting 3-year mortality in elderly patients with intertrochanteric fractures. BMC Geriatr 2023; 23:432. [PMID: 37438696 DOI: 10.1186/s12877-023-04065-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Accepted: 05/24/2023] [Indexed: 07/14/2023] Open
Abstract
BACKGROUND Hip fractures are common in elderly patients, and almost all the patients undergo surgery. This study aimed to develop a novel modified lymphocyte C-reactive protein (CRP) score (mLCS) to simply and conveniently predict 3-year mortality in elderly patients undergoing intertrochanteric fracture surgery. METHODS A retrospective study was conducted on elderly patients who underwent intertrochanteric fracture surgery between January 2014 and December 2017. The mLCS was developed according to the value of CRP and lymphocyte counts. Univariate and multivariate Cox regression analyses were used to identify independent risk factors for 3-year mortality after surgery. The performances of the lymphocyte CRP score (LCS) and mLCS to predict 3-year mortality were then compared using C-statistics, decision curve analysis (DCA), net reclassification index (NRI) and integrated discrimination improvement (IDI). RESULTS A total of 291 patients were enrolled, of whom 52 (17.9%) died within 3 years after surgery. In the multivariate Cox regression analysis, mLCS (hazard ratio (HR), 5.415; 95% confidence interval (CI), 1.743-16.822; P = 0.003) was significantly associated with postoperative 3-year mortality. The C-statistics of LCS and mLCS for predicting 3-year mortality were 0.644 and 0.686, respectively. The NRI (mLCS vs. LCS, 0.018) and IDI (mLCS vs. LCS, 0.017) indicated that the mLCS performed better than the LCS. DCA also showed that mLCS had a higher clinical net benefit. CONCLUSIONS mLCS is a promising predictor that can simply and conveniently predict 3-year mortality in elderly patients undergoing intertrochanteric fracture surgery.
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Affiliation(s)
- Zile He
- Department of Anesthesiology, The First Medical Center of Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China
- Department of Anesthesiology, Peking University People's Hospital, Beijing, China
| | - Chuangxin Zhang
- Chinese PLA Medical School, Beijing, 100853, China
- Department of Anesthesiology, The Fourth Medical Center of Chinese PLA General Hospital, Beijing, 100037, China
| | - Mingzi Ran
- Department of Anesthesiology, The Fourth Medical Center of Chinese PLA General Hospital, Beijing, 100037, China
| | - Xin Deng
- Department of Liver Transplantation and Hepatobiliary Surgery, Shandong Provincial Hospital, Shandong First Medical University, Jinan, China
| | - Zilin Wang
- Department of Anesthesiology, The First Medical Center of Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China
| | - Yanhong Liu
- Department of Anesthesiology, The First Medical Center of Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China
| | - Hao Li
- Department of Anesthesiology, The First Medical Center of Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China
| | - Jingsheng Lou
- Department of Anesthesiology, The First Medical Center of Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China
| | - Weidong Mi
- Department of Anesthesiology, The First Medical Center of Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China.
| | - Jiangbei Cao
- Department of Anesthesiology, The First Medical Center of Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China.
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Yi J, Xue J, Yang L, Xia L, He W. Predictive value of prognostic nutritional and systemic immune-inflammation indices for patients with microsatellite instability-high metastatic colorectal cancer receiving immunotherapy. Front Nutr 2023; 10:1094189. [PMID: 37275637 PMCID: PMC10232767 DOI: 10.3389/fnut.2023.1094189] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Accepted: 04/27/2023] [Indexed: 06/07/2023] Open
Abstract
Background The prognostic nutritional index (PNI) and systemic immune-inflammation index (SII) are indicators of nutritional immune status. They have been reported associated with clinical outcomes of various solid tumors. However, it is unclear whether they can serve as predictors for patients with microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC) receiving immunotherapy. Our objective was to study the prognostic value of PNI and SII in these patients. Methods Seventy-five MSI-H mCRC patients were enrolled in our study. Logistic regression analysis was used to identify features that influenced immunotherapy response. Survival differences between groups of mCRC patients were compared using the Kaplan-Meier method and log-rank test. The independent risk parameters for progression-free survival (PFS) and overall survival (OS) of patients with MSI-H mCRC were established by Cox proportional risk regression analysis. Results The optimal SII and PNI cutoff values were 409.6 and 51.35. Higher PNI (p = 0.012) and lower high-density lipoprotein cholesterol (HDLC, p = 0.012) were associated with a better immunotherapy response. SII (p = 0.031), cholesterol (CHO) (p = 0.007) and aspartate aminotransferase (AST) (p = 0.031) were independent prognostic factors correlated with OS. Higher PNI (p = 0.012) and lower AST (p = 0.049) were negative predictors of PFS. In addition, patients suffered from immune-related adverse events (irAEs) had a lower SII level (p = 0.04). Conclusion Higher AST and SII, and lower PNI predict worse outcomes in MSI-H mCRC patients undergoing immunotherapy. Moreover, patients with lower SII before immunotherapy suffered from irAEs more often.
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Affiliation(s)
- Jiahong Yi
- Department of VIP Region, Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Ju Xue
- Department of VIP Region, Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Lin Yang
- Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Liangping Xia
- Department of VIP Region, Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Wenzhuo He
- Department of VIP Region, Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China
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Tan X, Wang S, Xia H, Chen H, Xu J, Meng D, Wang Z, Li Y, Yang L, Jin Y. Prognosis prediction of icotinib as targeted therapy for advanced EGFR-positive non-small cell lung cancer patients. Invest New Drugs 2023:10.1007/s10637-023-01329-8. [PMID: 37140694 DOI: 10.1007/s10637-023-01329-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Accepted: 01/02/2023] [Indexed: 05/05/2023]
Abstract
Clinical trials on icotinib, a first-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), have shown promising results as targeted therapy for non-small cell lung cancer (NSCLC). This study aimed to establish an effective scoring system to predict the one-year progression-free survival (PFS) of advanced NSCLC patients with EGFR mutations treated with icotinib as targeted therapy. A total of 208 consecutive patients with advanced EGFR-positive NSCLC treated with icotinib were enrolled in this study. Baseline characteristics were collected within 30 days before icotinib treatment. PFS was taken as the primary endpoint and the response rate as the secondary endpoint. Least absolute shrinkage and selection operator (LASSO) regression analysis and Cox proportional hazards regression analysis were used to select the optimal predictors. We evaluated the scoring system using a five-fold cross-validation. PFS events occurred in 175 patients, with a median PFS of 9.9 months (interquartile range, 6.8-14.5). The objective response rate (ORR) was 36.1%, and the disease control rate (DCR) was 67.3%. The final ABC-Score consisted of three predictors: age, bone metastases and carbohydrate antigen 19-9 (CA19-9). Upon comparison of all three factors, the combined ABC-score (area under the curve (AUC)= 0.660) showed a better predictive accuracy than age (AUC = 0.573), bone metastases (AUC = 0.615), and CA19-9 (AUC = 0.608) individually. A five-fold cross-validation showed good discrimination with AUC = 0.623. The ABC-score developed in this study was significantly effective as a prognostic tool for icotinib in advanced NSCLC patients with EGFR mutations.
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Affiliation(s)
- Xueyun Tan
- Department of Respiratory and Critical Care Medicine, Hubei Province Clinical Research Center for Major Respiratory Disease, NHC Key Laboratory of Pulmonary Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, Hubei, China
- Hubei Province Engineering Research Center for Tumor-Targeted Biochemotherapy, MOE Key Laboratory of Biological Targeted Therapy, Tongji Medical College, Union Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Sufei Wang
- Department of Respiratory and Critical Care Medicine, Hubei Province Clinical Research Center for Major Respiratory Disease, NHC Key Laboratory of Pulmonary Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, Hubei, China
- Hubei Province Engineering Research Center for Tumor-Targeted Biochemotherapy, MOE Key Laboratory of Biological Targeted Therapy, Tongji Medical College, Union Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Hui Xia
- Department of Respiratory and Critical Care Medicine, Hubei Province Clinical Research Center for Major Respiratory Disease, NHC Key Laboratory of Pulmonary Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, Hubei, China
- Hubei Province Engineering Research Center for Tumor-Targeted Biochemotherapy, MOE Key Laboratory of Biological Targeted Therapy, Tongji Medical College, Union Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Hebing Chen
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, Hubei, China
| | - Juanjuan Xu
- Department of Respiratory and Critical Care Medicine, Hubei Province Clinical Research Center for Major Respiratory Disease, NHC Key Laboratory of Pulmonary Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, Hubei, China
- Hubei Province Engineering Research Center for Tumor-Targeted Biochemotherapy, MOE Key Laboratory of Biological Targeted Therapy, Tongji Medical College, Union Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Daquan Meng
- Department of Respiratory and Critical Care Medicine, Hubei Province Clinical Research Center for Major Respiratory Disease, NHC Key Laboratory of Pulmonary Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, Hubei, China
- Hubei Province Engineering Research Center for Tumor-Targeted Biochemotherapy, MOE Key Laboratory of Biological Targeted Therapy, Tongji Medical College, Union Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Zhihui Wang
- Department of Scientific Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Yan Li
- Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Lian Yang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, Hubei, China.
| | - Yang Jin
- Department of Respiratory and Critical Care Medicine, Hubei Province Clinical Research Center for Major Respiratory Disease, NHC Key Laboratory of Pulmonary Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, Hubei, China.
- Hubei Province Engineering Research Center for Tumor-Targeted Biochemotherapy, MOE Key Laboratory of Biological Targeted Therapy, Tongji Medical College, Union Hospital, Huazhong University of Science and Technology, Wuhan, China.
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Jain A, Zhang S, Shanley RM, Fujioka N, Kratzke RA, Patel MR, Kulkarni AA. Nonlinear association between body mass index and overall survival in advanced NSCLC patients treated with immune checkpoint blockade. Cancer Immunol Immunother 2023; 72:1225-1232. [PMID: 36383245 PMCID: PMC10992579 DOI: 10.1007/s00262-022-03320-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Accepted: 10/30/2022] [Indexed: 11/18/2022]
Abstract
BACKGROUND We investigated the association of body mass index (BMI) modeled as a continuous variable with survival outcomes in advanced non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICI). METHODS We performed a single-institution retrospective analysis of consecutively diagnosed locally advanced or metastatic NSCLC patients treated with single-agent ICI in the first line or recurrent setting. The primary outcome was overall survival (OS). Secondary outcomes were progression-free survival (PFS) and objective response rate (ORR). BMI was modeled using a four-knot restricted cubic spline. Multiple Cox regression was used for survival analysis. RESULTS Two hundred patients were included (female 54%; never smoker 12%). Adenocarcinoma was the most common histology (61%). Median age was 67 years, median BMI was 25.9 kg/m2, and 65% of patients had Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1. On multivariable analysis, only BMI and ECOG PS were independently associated with OS (p < 0.01). Mortality risk decreased as the BMI increased from 20 to 30 kg/m2 (HR 0.49, 95% CI 0.28-0.84); however, it was reversed as the BMI surpassed ~ 30 kg/m2. Compared to ECOG PS ≥ 2, patients with ECOG PS of 0-1 had a longer OS (HR 0.42, 95% CI 0.28-0.63). Similar trends were observed with PFS and ORR, but the strength of the association was weaker. CONCLUSION We observed a nonlinear association between BMI and OS following treatment with ICI in advanced NSCLC. Risk of death increases at both extremes of BMI with a nadir that exists around 30 kg/m2.
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Affiliation(s)
- Aditya Jain
- Division of Hematology, Oncology and Transplantation, University of Minnesota, 420 Delaware Street SE, Minneapolis, MN, 55455, USA
| | - Shijia Zhang
- Division of Hematology, Oncology and Transplantation, University of Minnesota, 420 Delaware Street SE, Minneapolis, MN, 55455, USA
| | - Ryan M Shanley
- Biostatistics Core, Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA
| | - Naomi Fujioka
- Division of Hematology, Oncology and Transplantation, University of Minnesota, 420 Delaware Street SE, Minneapolis, MN, 55455, USA
| | - Robert A Kratzke
- Division of Hematology, Oncology and Transplantation, University of Minnesota, 420 Delaware Street SE, Minneapolis, MN, 55455, USA
| | - Manish R Patel
- Division of Hematology, Oncology and Transplantation, University of Minnesota, 420 Delaware Street SE, Minneapolis, MN, 55455, USA
| | - Amit A Kulkarni
- Division of Hematology, Oncology and Transplantation, University of Minnesota, 420 Delaware Street SE, Minneapolis, MN, 55455, USA.
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Hernando-Calvo A, Mirallas O, Marmolejo D, Saavedra O, Vieito M, Assaf Pastrana JD, Aguilar S, Bescós C, Lorente J, Giralt J, Benavente S, Temprana-Salvador J, Alberola M, Dienstmann R, Garralda E, Felip E, Villacampa G, Brana I. Nutritional status associates with immunotherapy clinical outcomes in recurrent or metastatic head and neck squamous cell carcinoma patients. Oral Oncol 2023; 140:106364. [PMID: 36989964 DOI: 10.1016/j.oraloncology.2023.106364] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Revised: 02/04/2023] [Accepted: 03/05/2023] [Indexed: 03/29/2023]
Abstract
BACKGROUND Beyond programmed death-ligand 1 (PD-L1) assessed by the combined positive score (CPS) and tumor mutational burden (TMB), no other biomarkers are approved for immunotherapy interventions. Here, we investigated whether additional clinical and pathological variables may impact on immunotherapy outcomes in recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients. METHODS R/M HNSCC patients treated with immunotherapy were reviewed. Analyzed variables at baseline included: clinicopathological, laboratory, and variables reflecting the host nutritional status such as the prognostic nutritional index (PNI) and albumin. The primary endpoint was progression free survival (PFS). The secondary endpoints were overall survival (OS) and objective response rate (ORR). Univariable and multivariable Cox models were fitted and random forest algorithm was used to estimate the importance of each prognostic variable. RESULTS A total of 100 patients were treated with immunotherapy; 50% with single agent and 50% with experimental immunotherapy combinations. In the multivariable analysis, both ECOG performance status (HR: 1.73; 95%CI 1.07-2.82; p = 0.03) and PNI levels (10-point increments, HR: 0.66; 0.46-0.95; p = 0.03) were significantly associated with PFS. However, the derived neutrophil to lymphocyte ratio (dNLR) and lactate dehydrogenase (LDH) were not significantly associated with PFS (p-values > 0.15). In the OS analysis, albumin and PNI were the only statistically significant factors in the multivariable model (p < 0.001). CONCLUSIONS In our cohort, PNI and ECOG performance status were most strongly associated with PFS in R/M HNSCC patients treated with immunotherapy. These results suggest that parameters informative of nutritional status should be considered before immunotherapy.
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Li C, Fan Z, Guo W, Liang F, Mao X, Wu J, Wang H, Xu J, Wu D, Liu H, Wang L, Li F. Fibrinogen-to-prealbumin ratio: A new prognostic marker of resectable pancreatic cancer. Front Oncol 2023; 13:1149942. [PMID: 37051547 PMCID: PMC10083287 DOI: 10.3389/fonc.2023.1149942] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Accepted: 03/15/2023] [Indexed: 03/28/2023] Open
Abstract
BackgroundThe fibrinogen-to-prealbumin ratio (FPR), a novel immune-nutritional biomarker, has been reported to be associated with prognosis in several types of cancer, but the role of FPR in the prognosis of resectable pancreatic cancer has not been elucidated.MethodsA total of 263 patients with resectable pancreatic cancer were enrolled in this study and were randomly divided into a training cohort (n = 146) and a validation cohort (n = 117). Receiver operating characteristic curve (ROC) was used to calculate the cut-off values of immune-nutritional markers. The least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression were performed in the training cohort to identify the independent risk factors, based on which the nomogram was established. The performance of the nomogram was evaluated and validation by the training and validation cohort, respectively.ResultsThe optimal cutoff value for FPR was 0.29. Multivariate analysis revealed that FPR, controlling nutritional status (CONUT), carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA), and tumor node metastasis (TNM) stage were independent predictors of overall survival (OS). The nomogram was established by involving the five factors above. The C-index of the training cohort and validation cohort were 0.703 (95% CI: 0.0.646-0.761) and 0.728 (95% CI: 0.671-0.784). Decision curve analysis and time-dependent AUC showed that the nomogram had better predictive and discriminative ability than the conventional TNM stage.ConclusionFPR is a feasible biomarker for predicting prognosis in patients with resectable pancreatic cancer. The nomogram based on FPR is a useful tool for clinicians in making individualized treatment strategies and survival predictions.
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Affiliation(s)
- Chengqing Li
- Department of Pancreatic Surgery, General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Zhiyao Fan
- Department of Pancreatic Surgery, General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Wenyi Guo
- Department of Pancreatic Surgery, General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Feng Liang
- Department of General Surgery, Feicheng People’s Hospital, Taian, China
| | - Xincheng Mao
- Department of Hepatobiliary Surgery, General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Jiahao Wu
- Department of Pancreatic Surgery, General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Haodong Wang
- Department of Pancreatic Surgery, General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Jianwei Xu
- Department of Pancreatic Surgery, General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Dong Wu
- Department of Pancreatic Surgery, General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Han Liu
- Department of Pancreatic Surgery, General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Lei Wang
- Department of Pancreatic Surgery, General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- *Correspondence: Lei Wang, ; Feng Li,
| | - Feng Li
- Department of Pancreatic Surgery, General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- *Correspondence: Lei Wang, ; Feng Li,
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Wu Y, Yang J, Qiao X, Li Y, Zhao R, Lin T, Li X, Wang M. Use of the prognostic nutrition index as a predictive biomarker in small-cell lung cancer patients undergoing immune checkpoint inhibitor treatment in the Chinese alpine region. Front Oncol 2023; 13:1041140. [PMID: 37007079 PMCID: PMC10050450 DOI: 10.3389/fonc.2023.1041140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2022] [Accepted: 02/28/2023] [Indexed: 03/17/2023] Open
Abstract
BackgroundWhether the prognostic nutritional index (PNI), which is suggested to reflect systemic inflammation and nutritional status of patients, could be used as an effective prognostic factor for small-cell lung cancer (SCLC) has not yet been clarified. The purpose of this study was to verify the prognostic value of the PNI in SCLC patients treated with programmed cell death ligand-1/programmed cell death 1 (PD-L1/PD-1) inhibitors in the alpine region of China.MethodsSCLC patients treated with PD-L1/PD-1 inhibitors monotherapy or combined with chemotherapy between March 2017 and May 2020 were included. Based on the values of serum albumin and total lymphocyte count, the study population was divided into two groups: high and low PNI. The Kaplan-Meier method was used to compute the median survival time and the log-rank test was used to compare the two groups. To evaluate the prognostic value of the PNI, univariable and multivariable analyses of progression-free survival (PFS) and overall survival (OS) were performed. The correlations between PNI and DCR or ORR were calculated by Point biserial correlation analysis.ResultsOne hundred and forty patients were included in this study, of which, 60.0% were high PNI (PNI > 49.43) and 40.0% were low PNI (PNI ≤ 49.43). Results indicated that the high PNI group had better PFS and OS than the low PNI group in the patients who received PD-L1/PD-1 inhibitors monotherapy (median PFS: 11.0 vs. 4.8 months, p < 0.001 and median OS: 18.5 vs. 11.0 months, p = 0.004). Similarly, better PFS and OS were associated with an increase in PNI level in the patients who accepted PD-L1/PD-1 inhibitors combined with chemotherapy (median PFS: 11.0 vs. 5.3 months, p < 0.001 and median OS: 17.9 vs. 12.6 months, p = 0.005). Multivariate Cox-regression model showed that high PNI was significantly related to better PFS and OS in patients who accepted PD-L1/PD-1 inhibitors monotherapy or combined with chemotherapy (PD-L1/PD-1 inhibitors monotherapy: PFS: HR = 0.23, 95% CI: 0.10–0.52, p < 0.001 and OS: HR = 0.13, 95% CI: 0.03–0.55, p = 0.006; PD-L1/PD-1 inhibitors combined with chemotherapy: PFS: HR = 0.34, 95% CI: 0.19–0.61, p < 0.001 and OS: HR = 0.53, 95% CI: 0.29–0.97, p = 0.040, respectively). Additionally, Point biserial correlation analysis between PNI and disease control rate (DCR) showed that PNI status was positively correlated with DCR in SCLC patients receiving PD-L1/PD-1 inhibitors or combined with chemotherapy (r = 0.351, p < 0.001; r = 0.285, p < 0.001, respectively).ConcussionsPNI may be a promising biomarker of treatment efficacy and prognosis in SCLC patients treated with PD-L1/PD-1 inhibitors in the alpine region of China.
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Affiliation(s)
- Yunjiao Wu
- Department of Respiratory Medical Oncology, Harbin Medical University Cancer Hospital, Heilongjiang, Harbin, China
| | - Jing Yang
- Chongqing Engineering Research Center for Processing and Storage of Distinct Agricultural Products, Chongqing Technology and Business University, Chongqing, China
| | - Xinyi Qiao
- Department of Respiratory Medical Oncology, Harbin Medical University Cancer Hospital, Heilongjiang, Harbin, China
| | - Yingjie Li
- Department of Respiratory Medical Oncology, Harbin Medical University Cancer Hospital, Heilongjiang, Harbin, China
| | - Rui Zhao
- Department of Respiratory Medical Oncology, Harbin Medical University Cancer Hospital, Heilongjiang, Harbin, China
| | - Tie Lin
- Department of Surgery, The First Affiliated Hospital of Harbin Medical University, Heilongjiang, Harbin, China
| | - Xiaoli Li
- Department of Respiratory Medical Oncology, Harbin Medical University Cancer Hospital, Heilongjiang, Harbin, China
| | - Meng Wang
- Department of Respiratory Medical Oncology, Harbin Medical University Cancer Hospital, Heilongjiang, Harbin, China
- *Correspondence: Meng Wang,
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Pan C, Wu QV, Voutsinas J, Houlton JJ, Barber B, Rizvi ZH, Marchiano E, Futran N, Laramore GE, Liao JJ, Parvathaneni U, Martins RG, Fromm JR, Rodriguez CP. Peripheral lymphocytes and lactate dehydrogenase correlate with response and survival in head and neck cancers treated with immune checkpoint inhibitors. Cancer Med 2023; 12:9384-9391. [PMID: 36806947 PMCID: PMC10166901 DOI: 10.1002/cam4.5697] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 01/31/2023] [Accepted: 02/03/2023] [Indexed: 02/23/2023] Open
Abstract
BACKGROUND Little is known regarding associations between peripheral blood biomarkers (PBBMs) and survival, response, and toxicity in recurrent/metastatic head and neck squamous cell carcinomas (R/M HNSCC) treated with immune checkpoint inhibitors (ICIs). METHODS In this single-institution retrospective cohort study, a dataset of patients with R/M HNSCC treated with ICIs between 08/2012-03/2021 was established, including demographic and clinicopathologic characteristics. Pretreatment PBBMs were collected and evaluated for associations with grade ≥3 adverse events (G ≥ 3AE) by CTCAEv5, objective response (ORR) by RECIST 1.1, overall survival (OS), and progression-free survival (PFS). Multivariable models for each outcome were created using elastic net variable selection. RESULTS Our study included 186 patients, with 51 (27%) demonstrating complete or partial response to immunotherapy. Multivariable models adjusted for ECOG performance status (PS), p16, and smoking demonstrated that pretreatment higher LDH and absolute neutrophils, as well as lower percent lymphocytes correlated with worse OS and PFS. Higher LDH and lower % lymphocytes also correlated with worse ORR. CONCLUSIONS In the largest study to date examining PBBMs in ICI-treated R/M HNSCCs, our variable selection method revealed PBBMs prognostic for survival and response to immunotherapy. These biomarkers warrant further investigation in a prospective study along with validation with CPS biomarker.
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Affiliation(s)
- Cassie Pan
- Department of Otolaryngology-Head and Neck Surgery, University of Washington, Seattle, Washington, USA
| | - Qian Vicky Wu
- Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA
| | - Jenna Voutsinas
- Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA
| | | | - Brittany Barber
- Department of Otolaryngology-Head and Neck Surgery, University of Washington, Seattle, Washington, USA
| | - Zain H Rizvi
- Department of Otolaryngology-Head and Neck Surgery, University of Washington, Seattle, Washington, USA
| | - Emily Marchiano
- Department of Otolaryngology-Head and Neck Surgery, University of Washington, Seattle, Washington, USA
| | - Neal Futran
- Department of Otolaryngology-Head and Neck Surgery, University of Washington, Seattle, Washington, USA
| | - George E Laramore
- Department of Radiation Oncology, University of Washington, Seattle, Washington, USA
| | - Jay J Liao
- Department of Radiation Oncology, University of Washington, Seattle, Washington, USA
| | - Upendra Parvathaneni
- Department of Radiation Oncology, University of Washington, Seattle, Washington, USA
| | - Renato G Martins
- Division of Hematology, Oncology and Palliative Care, Department of Medicine, Virginia Commonwealth University, Richmond, Virginia, USA
| | - Jonathan R Fromm
- Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA
| | - Cristina P Rodriguez
- Division of Oncology, Department of Medicine, University of Washington, Seattle, Washington, USA
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Trinkner P, Günther S, Monsef I, Kerschbaum E, von Bergwelt-Baildon M, Cordas Dos Santos DM, Theurich S. Survival and immunotoxicities in association with sex-specific body composition patterns of cancer patients undergoing immune-checkpoint inhibitor therapy - A systematic review and meta-analysis. Eur J Cancer 2023; 184:151-171. [PMID: 36931074 DOI: 10.1016/j.ejca.2023.01.030] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Revised: 01/28/2023] [Accepted: 01/30/2023] [Indexed: 02/19/2023]
Abstract
BACKGROUND Imbalanced body composition is mechanistically connected to dysregulated immune activities. Whether overweight/obesity or sarcopenia has an impact on treatment results in cancer patients undergoing immune checkpoint inhibitor (ICI) therapy is currently under debate. We aimed to answer if survival rates and occurrence of immune-related adverse events (irAEs) were different in obese or sarcopenic patients. METHODS A systematic search was conducted in PubMed, Embase and CENTRAL for all records published until July 2022 using specific search terms for body composition in combination with terms for ICI regimens. Two authors screened independently. All studies that reported on body mass index or sarcopenia measures were selected for further analysis. RESULTS 48 studies reporting on overweight/obesity comprising of 19,767 patients, and 32 studies reporting on sarcopenia comprising of 3193 patients fulfilled the inclusion criteria. In the entire cohort, overweight/obesity was significantly associated with better progression-free survival (PFS; p = 0.009) and overall survival (OS; p <0.00001). Subgroup analyses stratified by sex revealed that overweight/obese males had the strongest survival benefit (PFS: p = 0.05; OS: p = 0.0005), and overweight/obese female patients did not show any. However, overweight/obese patients of both sexes had a higher risk to develop irAEs grade ≥3 (p = 0.0009). Sarcopenic patients showed significantly shorter PFS (p <0.0001) and OS (p <0.0001). The frequency of irAEs did not differ between sarcopenic and non-sarcopenic patients. CONCLUSION This meta-analysis suggests that body composition is associated in a sex-specific manner with survival and irAEs in cancer patients undergoing ICI treatment.
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Affiliation(s)
- Paul Trinkner
- Department of Medicine III, University Hospital, LMU Munich, Munich, Germany; Cancer- and Immunometabolism Research Group, Gene Center, LMU Munich, Munich, Germany
| | - Sophie Günther
- Department of Medicine III, University Hospital, LMU Munich, Munich, Germany; Cancer- and Immunometabolism Research Group, Gene Center, LMU Munich, Munich, Germany
| | - Ina Monsef
- Evidence-based Medicine, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Faculty of Medicine and University Hospital Cologne, University of Cologne, Germany
| | - Eva Kerschbaum
- Comprehensive Cancer Center Munich (CCCM), Munich, Germany
| | - Michael von Bergwelt-Baildon
- Department of Medicine III, University Hospital, LMU Munich, Munich, Germany; Comprehensive Cancer Center Munich (CCCM), Munich, Germany; German Cancer Consortium (DKTK), Partner Site Munich, and German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - David M Cordas Dos Santos
- Department of Medicine III, University Hospital, LMU Munich, Munich, Germany; Cancer- and Immunometabolism Research Group, Gene Center, LMU Munich, Munich, Germany; German Cancer Consortium (DKTK), Partner Site Munich, and German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Sebastian Theurich
- Department of Medicine III, University Hospital, LMU Munich, Munich, Germany; Cancer- and Immunometabolism Research Group, Gene Center, LMU Munich, Munich, Germany; German Cancer Consortium (DKTK), Partner Site Munich, and German Cancer Research Center (DKFZ), Heidelberg, Germany.
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The Geriatric Nutritional Risk Index (GNRI) as a Prognostic Biomarker for Immune Checkpoint Inhibitor Response in Recurrent and/or Metastatic Head and Neck Cancer. Nutrients 2023; 15:nu15040880. [PMID: 36839241 PMCID: PMC9961934 DOI: 10.3390/nu15040880] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2023] [Revised: 02/01/2023] [Accepted: 02/07/2023] [Indexed: 02/12/2023] Open
Abstract
Malnutrition is a frequent comorbidity in head and neck cancer patients and has been shown to impair immunotherapy response in other cancer types. The geriatric nutritional risk index (GNRI) assesses malnutrition using the patient's ideal weight, actual weight, and serum albumin. The aim of this study was to evaluate the prognostic relevance of malnutrition as determined by the GNRI for the response to immunotherapy in recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC). A total of 162 patients with R/M HNSCC who received immune checkpoint inhibitors were included. The associations between the GNRI and progression-free survival (PFS), overall survival (OS), and the disease control rate (DCR) were computed. Univariable analysis showed worse PFS for GNRI ≤ 98 (p < 0.001), ECOG performance status (PS) ≥ 2 (p = 0.012), and enteral (p = 0.009) and parenteral (p = 0.015) nutritional supplementation, and worse OS for GNRI < 92 (p < 0.001), ECOG PS ≥ 2 (p < 0.001), and enteral (p = 0.008) and parenteral (p = 0.023) nutritional supplementation. In our multivariable model, GNRI ≤ 98 (p = 0.012) and ECOG PS ≥ 2 (p = 0.025) were independent prognostic factors for PFS. For OS, GNRI < 92 (p < 0.001) and ECOG PS ≥ 2 (p < 0.001) were independent prognostic factors. A GNRI ≤ 98 was significantly associated with a lower DCR compared to a GNRI > 98 (p = 0.001). In conclusion, our findings suggest that the GNRI may be an effective predictor for response to immunotherapy in R/M HNSCC.
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Leis C, Arthur AE, Chen X, Greene MW, Frugé AD. Systematic Review of Nutrition Interventions to Improve Short Term Outcomes in Head and Neck Cancer Patients. Cancers (Basel) 2023; 15:822. [PMID: 36765780 PMCID: PMC9913111 DOI: 10.3390/cancers15030822] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Revised: 01/18/2023] [Accepted: 01/27/2023] [Indexed: 02/02/2023] Open
Abstract
Head and neck cancer (HNC) is associated with high rates of malnutrition. We conducted a systematic review and descriptive analysis to determine the effects of nutrition interventions on the nutrition status, quality of life (QOL), and treatment tolerance of HNC patients. PubMed, Web of Science, and Embase were searched to include all potentially relevant studies published between 2006-2022. Meta-analysis was not conducted due to heterogeneity of study designs and outcomes reported. Studies were categorized as nutrition interventions: (1) with oral nutrition supplements (ONS) and medical nutrition therapy (MNT) delivered by an RD; (2) with enteral nutrition (EN) support and MNT delivered by an RD; (3) with motivational interviewing and no ONS or EN; and (4) with ONS and no RD. Seven articles met inclusion criteria. Studies measured outcomes from immediately following treatment to 12 months post-treatment. Interventions resulted in benefits to lean mass/weight maintenance (three studies), QOL (two studies), nutrient intake adequacy (one study) and treatment tolerance (two studies). Nutrition counseling by a registered dietitian leads to improved nutrition status and QOL. Further research is needed to determine best practices related to timing of initiation, duration of nutrition intervention, as well as frequency of dietitian follow-up.
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Affiliation(s)
- Claire Leis
- Department of Nutritional Sciences, Auburn University, Auburn, AL 36849, USA
| | - Anna E. Arthur
- Department of Dietetics and Nutrition, University of Kansas Medical Center, Kansas City, KS 66160, USA
| | - Xin Chen
- Department of Dietetics and Nutrition, University of Kansas Medical Center, Kansas City, KS 66160, USA
| | - Michael W. Greene
- Department of Nutritional Sciences, Auburn University, Auburn, AL 36849, USA
| | - Andrew D. Frugé
- College of Nursing, Auburn University, Auburn, AL 36849, USA
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Antoun S, Lanoy E, Ammari S, Farhane S, Martin L, Robert C, Planchard D, Routier E, Voisin AL, Messayke S, Champiat S, Michot JM, Laghouati S, Lambotte O, Marabelle A, Baracos V. Protective effect of obesity on survival in cancers treated with immunotherapy vanishes when controlling for type of cancer, weight loss and reduced skeletal muscle. Eur J Cancer 2023; 178:49-59. [PMID: 36403367 DOI: 10.1016/j.ejca.2022.10.013] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Revised: 10/16/2022] [Accepted: 10/19/2022] [Indexed: 11/30/2022]
Abstract
INTRODUCTION Association of high body mass index (BMI) with longer survival has been reported in patients on immune checkpoint inhibitors (ICIs), but results are inconsistent. This 'obesity paradox' is potentially confounded by the effects of BMI change over time and of skeletal muscle depletion. METHODS We conducted a secondary analysis of a prospective cohort, including consecutive patients receiving ICI treatment for melanoma (n = 411) and non-small cell lung cancer (NSCLC) (n = 389) in routine care. RESULTS In the univariable analysis of the entire population, overweight/obesity (BMI ≥ 25 kg/m2) was associated with longer survival (p < 0.01); however, this effect was limited to NSCLC (p < 0.01) and was absent in melanoma. Weight loss (WL) and reduced skeletal muscle mass were observed in patients within all BMI categories. WL was associated with shorter survival in multivariable analysis in both tumour sites (p < 0.01), and for NSCLC, BMI lost significance when WL was included (p = 0.13). In models further adjusted for CT-defined skeletal muscle mass, WL retained significance for both tumour types (p < 0.01), and reduced skeletal muscle only for NSCLC (p = 0.02) was associated with shorter survival. WL retained significance when biomarkers (lactate dehydrogenase enzyme, albumin and derived neutrophil to lymphocyte ratio) were added to the multivariable model. CONCLUSIONS The so-called 'obesity paradox', counterintuitive association between high BMI and longer survival, vanished when controlling for confounders, such as type of cancer, and manifestations of depletion (WL and reduced skeletal muscle mass).
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Affiliation(s)
- Sami Antoun
- Département Interdisciplinaire d'Organisation Du Parcours Patient, Gustave Roussy, Université Paris-Saclay, F-94800, Villejuif, France.
| | - Emilie Lanoy
- Département Interdisciplinaire d'Organisation Du Parcours Patient, Gustave Roussy, Université Paris-Saclay, F-94800, Villejuif, France
| | - Samy Ammari
- Département d'Imagerie Médicale BIOMAPS, UMR1281 INSERM, CEA, CNRS, Gustave Roussy, Université Paris-Saclay, F-94800, Villejuif, France; ELSAN Département de Radiologie, Institut de Cancérologie Paris Nord, Sarcelles, France
| | - Siham Farhane
- Département des Innovations Thérapeutiques et Essais Précoces, Gustave Roussy, Université Paris-Saclay, F-94800, Villejuif, France
| | - Lisa Martin
- Department of Oncology, University of Alberta, Canada
| | - Caroline Robert
- Département d'Oncologie Medicale, Gustave Roussy, Université Paris-Saclay, F-94800, Villejuif, France
| | - David Planchard
- Département d'Oncologie Medicale, Gustave Roussy, Université Paris-Saclay, F-94800, Villejuif, France
| | - Emilie Routier
- Département d'Oncologie Medicale, Gustave Roussy, Université Paris-Saclay, F-94800, Villejuif, France
| | - Anne Laure Voisin
- Unité de Pharmacovigilance, Gustave Roussy, Université Paris-Saclay, F-94800, Villejuif, France
| | - Sabine Messayke
- Unité de Pharmacovigilance, Gustave Roussy, Université Paris-Saclay, F-94800, Villejuif, France
| | - Stephane Champiat
- Département des Innovations Thérapeutiques et Essais Précoces, Gustave Roussy, Université Paris-Saclay, F-94800, Villejuif, France
| | - Jean Marie Michot
- Département des Innovations Thérapeutiques et Essais Précoces, Gustave Roussy, Université Paris-Saclay, F-94800, Villejuif, France
| | - Salim Laghouati
- Unité de Pharmacovigilance, Gustave Roussy, Université Paris-Saclay, F-94800, Villejuif, France
| | - Olivier Lambotte
- Université Paris Saclay, UMR1184 CEA, Inserm, Le Kremlin-Bicêtre, France; Service de Médecine Interne et Immunologie Clinique, Hôpital Bicêtre, Université Paris Saclay, AP-HP, Le Kremlin-Bicêtre, France
| | - Aurélien Marabelle
- Département des Innovations Thérapeutiques et Essais Précoces, Gustave Roussy, Université Paris-Saclay, F-94800, Villejuif, France
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Wang EY, Chen MK, Hsieh MY, Kor CT, Liu YT. Relationship between Preoperative Nutritional Status and Clinical Outcomes in Patients with Head and Neck Cancer. Nutrients 2022; 14:nu14245331. [PMID: 36558490 PMCID: PMC9782741 DOI: 10.3390/nu14245331] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Revised: 12/06/2022] [Accepted: 12/10/2022] [Indexed: 12/23/2022] Open
Abstract
The nutritional status in cancer patients is related to cancer survival and surgical outcome. The objective of this study was to examine the relationship between preoperative prognostic nutritional index (PNI) and post-operative clinical outcomes in head and neck cancer (HNC) patients. A total of 1282 head and neck cancer patients receiving surgical resection in Changhua Christian Hospital between 1 January 2010 and 30 August 2021 were recruited in the final analysis after undergoing propensity score matching analysis. The logistic regression model was used to assess the association of the PNI group with overall and various complications. The patients in the high PNI group had a significant lower incidence of overall complications, medical complications, and pulmonary complications; but not significant surgical complications. The high PNI group had lower mortality risk. The results in this study revealed that PNI score was a significant independent predictor of postoperative complications in HNC patients undergoing surgical resection. We recommend preoperative testing and evaluation of HNC patients to identify low PNI and high-risk groups for postoperative surveillance.
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Affiliation(s)
- En-Ying Wang
- Department of Otorhinolaryngology, Head and Neck Surgery, Changhua Christian Hospital, Changhua 500, Taiwan
| | - Mu-Kuan Chen
- Department of Otorhinolaryngology, Head and Neck Surgery, Changhua Christian Hospital, Changhua 500, Taiwan
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung 402, Taiwan
| | - Ming-Yu Hsieh
- Department of Otorhinolaryngology, Head and Neck Surgery, Changhua Christian Hospital, Changhua 500, Taiwan
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung 402, Taiwan
| | - Chew-Teng Kor
- Big Data Center, Changhua Christian Hospital, Changhua 500, Taiwan
- Graduate Institute of Statistics and Information Science, National Changhua University of Education, Changhua 500, Taiwan
| | - Yen-Tze Liu
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung 402, Taiwan
- Department of Family Medicine, Changhua Christian Hospital, Changhua 500, Taiwan
- Oral Cancer Research Center, Changhua Christian Hospital, Changhua 500, Taiwan
- Correspondence: ; Tel.: +886-4-7238595 (ext. 3267)
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Kageyama S, Yoshida T, Kobayashi K, Wada A, Nagasawa M, Kubota S, Kusaba T, Jo F, Nakagawa S, Johnin K, Narita M, Kawauchi A. Prognostic nutritional index of early post-pembrolizumab therapy predicts long-term survival in patients with advanced urothelial carcinoma. Oncol Lett 2022; 25:49. [PMID: 36644144 PMCID: PMC9811626 DOI: 10.3892/ol.2022.13635] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Accepted: 11/07/2022] [Indexed: 12/23/2022] Open
Abstract
Pembrolizumab has been widely used to treat advanced urothelial carcinoma that has progressed after first-line platinum-based chemotherapy. Because its clinical benefits are limited, biomarkers that can predict a good response to pembrolizumab are required. The prognostic nutritional index (PNI), calculated using the serum albumin level and peripheral lymphocyte count, has been evaluated as a predictive biomarker in cancer immunotherapy. The present study investigated the application of PNI as a predictive biomarker for pembrolizumab response in patients with advanced urothelial cancer. A retrospective study was conducted on 34 patients treated with pembrolizumab at Shiga University of Medical Science Hospital between January 2018 and July 2022. The posttreatment PNI (post-PNI) was calculated within 2 months of starting pembrolizumab. The present study investigated the association between post-PNI and objective response, overall survival (OS) and progression-free survival (PFS). The patient cohort was stratified into two categories, high and low post-PNI groups, with a cutoff value of post-PNI at 40. The higher post-PNI group demonstrated a better disease control rate than the lower post-PNI group (complete response + partial response + stable disease, 75 vs. 21%, P=0.004). Regarding median OS, the higher post-PNI group exhibited a significantly longer survival time than the lower post-PNI group (23.1 vs. 2.9 months, P<0.001). Similarly, the higher post-PNI group exhibited a significantly longer PFS than the lower post-PNI group (10.2 vs.1.9 months, P<0.001). Multivariate analysis showed that a higher post-PNI value was an independent predictor for OS (hazard ratio, 0.04; 95% confidence interval, 0.01-0.14; P<0.001) and PFS (hazard ratio, 0.12; 95% confidence interval, 0.04-0.35; P<0.001). The present study indicated that the post-PNI was a predictor of favorable clinical outcomes in patients treated with pembrolizumab for advanced urothelial carcinoma.
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Affiliation(s)
- Susumu Kageyama
- Department of Urology, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan,Correspondence to: Dr Susumu Kageyama, Department of Urology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan, E-mail:
| | - Tetsuya Yoshida
- Department of Urology, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan
| | - Kenichi Kobayashi
- Department of Urology, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan
| | - Akinori Wada
- Department of Urology, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan
| | - Masayuki Nagasawa
- Department of Urology, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan
| | - Shigehisa Kubota
- Department of Urology, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan
| | - Takuto Kusaba
- Department of Urology, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan
| | - Fumiyasu Jo
- Department of Urology, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan
| | - Shota Nakagawa
- Department of Urology, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan
| | - Kazuyoshi Johnin
- Department of Urology, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan
| | - Mitsuhiro Narita
- Department of Urology, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan
| | - Akihiro Kawauchi
- Department of Urology, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan
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Parosanu A, Stanciu IM, Pirlog C, Orlov Slavu C, Cotan H, Iaciu C, Popa AM, Olaru M, Moldoveanu O, Catalin B, Nitipir C. Prognostic Models for Renal Cell Carcinoma in the Era of Immune Checkpoint Therapy. Cureus 2022; 14:e30821. [DOI: 10.7759/cureus.30821] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/29/2022] [Indexed: 11/06/2022] Open
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Wu B, Ni LQ, Wang Y, Yang HH, Zhao SK. Low prognostic nutritional index is associated with poor outcome in middle-aged and elderly patients with non-metastatic nasopharyngeal carcinoma: a retrospective cohort study. Support Care Cancer 2022; 30:8895-8904. [PMID: 35879471 DOI: 10.1007/s00520-022-07286-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Accepted: 07/14/2022] [Indexed: 11/25/2022]
Abstract
BACKGROUND Prognostic nutritional index (PNI) and age are effective prognostic factors for patients with non-metastatic nasopharyngeal carcinoma (NPC), and an interaction between them may exist. However, the age cutoff value is generally set at 45 years in current studies. The clinical implications of PNI in middle-aged and elderly patients are unclear. Therefore, we aimed to uncover this issue. PATIENTS AND METHODS We retrospectively collected data from 132 middle-aged and elderly (≥ 45 years old) patients with non-metastatic NPC. The association between covariates and the PNI was analyzed using 2 or t-test. The effect of PNI on the prognosis was evaluated using univariate and multivariate Cox regression analyses. Unadjusted and multivariate-adjusted models were applied. Stratified and interactive analyses were performed to investigate the potential source of heterogeneity. RESULTS Median age (61.0 years versus 59.5 years) and the proportion of patients aged ≥ 60 years (57.6% versus 50.0%) in the low-PNI group were higher than those in the high-PNI group (P > 0.05). The patients with a low PNI had shorter overall survival (OS) (hazard ratio (HR) = 0.86, 95% confidence interval (CI) = 0.80-0.93; P < 0.001) and progression-free survival (PFS) (HR = 0.93, 95% CI = 0.87-0.99; P = 0.034). The results remained stable after three adjusted models of covariates, including age (P < 0.05). No significant interactions were observed in middle-aged (45-59 years) and elderly (≥ 60 years) subgroups for OS and PFS (P for interaction > 0.05). CONCLUSION Although there is an interaction between PNI and age, PNI is an independent prognostic factor in middle-aged and elderly patients with non-metastatic NPC.
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Affiliation(s)
- Bo Wu
- Department of Radiotherapy, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, China
| | - Ling-Qin Ni
- Department of Radiotherapy, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, China
| | - Yong Wang
- Department of Radiotherapy, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, China
| | - Hai-Hua Yang
- Department of Radiotherapy, Taizhou Hospital, Linhai, Zhejiang, China
| | - Shan-Kun Zhao
- Department of Urology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, China.
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Ni L, Huang J, Ding J, Kou J, Shao T, Li J, Gao L, Zheng W, Wu Z. Prognostic Nutritional Index Predicts Response and Prognosis in Cancer Patients Treated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis. Front Nutr 2022; 9:823087. [PMID: 35938131 PMCID: PMC9353139 DOI: 10.3389/fnut.2022.823087] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Accepted: 06/14/2022] [Indexed: 12/12/2022] Open
Abstract
Objective To investigate the association between pretreatment prognostic nutritional index (PNI) and clinical survival outcomes for advanced-stage cancer patients treated with immune checkpoint inhibitors (ICIs). Methods We conducted a comprehensive literature search to identify eligible studies concerning the relationship between pretreatment PNI and survival outcomes in advanced cancer patients treated with ICIs. Published data were extracted and pooled odds ratio (pOR) for objective response rate (ORR), disease control rate (DCR), and pooled hazard ratio (pHR) for overall survival (OS), progressive-free survival (PFS), along with 95% confidence intervals (95% CIs) were calculated. Results Twelve studies with 1,359 participants were included in our study. A higher level of PNI indicated a greater ORR (pOR = 2.17, 95% CI = 1.52–3.10) and favorable DCR (pOR = 2.48, 95% CI = 1.87–3.29). Low PNI was associated with a shorter OS (pHR = 2.24, 95% CI = 1.57–3.20) and unfavorable PFS (pHR = 1.61, 95% CI = 1.37–1.88). Conclusion Low PNI might be an effective biomarker of poor tumor response and adverse prognosis of advanced cancer patients with ICIs. Further studies are needed to verify the prognostic value of PNI in clinical practice.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Zhen Wu
- Zhen Wu, , orcid.org/0000-0002-1140-273X
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41
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Immune biomarkers are associated with poststroke fatigue at six months in patients with ischemic stroke. J Clin Neurosci 2022; 101:228-233. [DOI: 10.1016/j.jocn.2022.05.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Revised: 05/04/2022] [Accepted: 05/23/2022] [Indexed: 11/18/2022]
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Yeung C, Kartolo A, Holstead R, Moffat GT, Hanna L, Hopman W, Baetz T. No association between BMI and immunotoxicity or clinical outcomes for immune checkpoint inhibitors. Immunotherapy 2022; 14:765-776. [PMID: 35695057 DOI: 10.2217/imt-2021-0250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Background: The impact of BMI on immune checkpoint inhibitor toxicity and efficacy has not been clearly characterized. Methods: The authors conducted a retrospective single-center study of patients with advanced unresectable/metastatic cancer initiated on immune checkpoint inhibitors. Results: Of the 409 patients included in the study, 115 (28%) had a BMI ≥30. There was no difference in the development of immune-related adverse events, treatment response or overall survival with respect to BMI <30 versus ≥30 for the whole study population or the melanoma subgroup. Conclusion: Patients with BMI in the obese range (≥30) were not at increased risk of immunotoxicity. Furthermore, BMI was not correlated with treatment response or overall survival in patients receiving immune checkpoint inhibitors.
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Affiliation(s)
- Cynthia Yeung
- Department of Oncology, Kingston Health Sciences Centre, Kingston, ON, K7L 2V7, Canada
| | - Adi Kartolo
- Department of Oncology, Kingston Health Sciences Centre, Kingston, ON, K7L 2V7, Canada
| | - Ryan Holstead
- Department of Oncology, Kingston Health Sciences Centre, Kingston, ON, K7L 2V7, Canada
| | - Gordon Taylor Moffat
- Department of Oncology, Kingston Health Sciences Centre, Kingston, ON, K7L 2V7, Canada
| | - Lilian Hanna
- Department of Oncology, Kingston Health Sciences Centre, Kingston, ON, K7L 2V7, Canada
| | - Wilma Hopman
- Department of Oncology, Kingston Health Sciences Centre, Kingston, ON, K7L 2V7, Canada
| | - Tara Baetz
- Department of Oncology, Kingston Health Sciences Centre, Kingston, ON, K7L 2V7, Canada
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Guo Y, Wei L, Patel SH, Lopez G, Grogan M, Li M, Haddad T, Johns A, Ganesan LP, Yang Y, Spakowicz DJ, Shields PG, He K, Bertino EM, Otterson GA, Carbone DP, Presley C, Kulp SK, Mace TA, Coss CC, Phelps MA, Owen DH. Serum Albumin: Early Prognostic Marker of Benefit for Immune Checkpoint Inhibitor Monotherapy But Not Chemoimmunotherapy. Clin Lung Cancer 2022; 23:345-355. [PMID: 35131184 PMCID: PMC9149057 DOI: 10.1016/j.cllc.2021.12.010] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2021] [Revised: 12/07/2021] [Accepted: 12/28/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUND Cancer cachexia exhibits decreased albumin and associates with short overall survival (OS) in patients with non-small cell lung cancer (NSCLC), but whether on-treatment albumin changes associate with OS in NSCLC patients treated with immune checkpoint inhibitors (ICIs) and combination chemoimmunotherapy has not been thoroughly evaluated. PATIENTS AND METHODS We conducted a single-center retrospective study of patients with advanced NSCLC who received first-line ICI with or without chemotherapy between 2013 and 2020. The association of pretreatment albumin and early albumin changes with OS was evaluated using Kaplan-Meier method and Cox regression models. RESULTS A total of 210 patients were included: 109 in ICI cohort and 101 in ICI + Chemo cohort. Within a median of 21 days from treatment initiation, patients with ≥ 10% of albumin decrease had significantly shorter OS compared to patients without albumin decrease in ICI cohort. Pretreatment albumin and albumin decrease within the first or second cycle of treatment were significantly and independently associated with OS in ICI cohort, but not in ICI + Chemo cohort. The lack of association between albumin and OS with the addition of chemotherapy was more pronounced among patients with ≥ 1% PD-L1 expression in subgroup analysis. CONCLUSION Pretreatment serum albumin and early albumin decrease in ICI monotherapy was significantly associated with OS in advanced NSCLC. Early albumin change, as a routine lab value tested in clinic, may be combined with established biomarkers to improve outcome predictions of ICI monotherapy. The underlying mechanism of the observed association between decreased albumin and ICI resistance warrants further investigation.
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Affiliation(s)
- Yizhen Guo
- Division of Pharmaceutics and Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH
| | - Lai Wei
- Center for Biostatistics, Department of Biomedical Informatics, College of Medicine, The Ohio State University, Columbus, OH
| | - Sandip H Patel
- Division of Medical Oncology, Ohio State University Wexner Medical Center, James Cancer Hospital and Solove Research Institute, Columbus, OH
| | - Gabrielle Lopez
- Division of Medical Oncology, Ohio State University Wexner Medical Center, James Cancer Hospital and Solove Research Institute, Columbus, OH
| | - Madison Grogan
- Division of Medical Oncology, Ohio State University Wexner Medical Center, James Cancer Hospital and Solove Research Institute, Columbus, OH
| | - Mingjia Li
- Department of Internal Medicine, Ohio State University Wexner Medical Center, James Cancer Hospital and Solove Research Institute, Columbus, OH
| | - Tyler Haddad
- Department of Internal Medicine, Ohio State University Wexner Medical Center, James Cancer Hospital and Solove Research Institute, Columbus, OH
| | - Andrew Johns
- Department of Internal Medicine, Ohio State University Wexner Medical Center, James Cancer Hospital and Solove Research Institute, Columbus, OH
| | - Latha P Ganesan
- Department of Internal Medicine, Ohio State University Wexner Medical Center, James Cancer Hospital and Solove Research Institute, Columbus, OH
| | - Yiping Yang
- Division of Hematology, Ohio State University Wexner Medical Center, James Cancer Hospital and Solove Research Institute, Columbus, OH
| | - Daniel J Spakowicz
- Division of Medical Oncology, Ohio State University Wexner Medical Center, James Cancer Hospital and Solove Research Institute, Columbus, OH
| | - Peter G Shields
- Division of Medical Oncology, Ohio State University Wexner Medical Center, James Cancer Hospital and Solove Research Institute, Columbus, OH
| | - Kai He
- Division of Medical Oncology, Ohio State University Wexner Medical Center, James Cancer Hospital and Solove Research Institute, Columbus, OH
| | - Erin M Bertino
- Division of Medical Oncology, Ohio State University Wexner Medical Center, James Cancer Hospital and Solove Research Institute, Columbus, OH
| | - Gregory A Otterson
- Division of Medical Oncology, Ohio State University Wexner Medical Center, James Cancer Hospital and Solove Research Institute, Columbus, OH
| | - David P Carbone
- Division of Medical Oncology, Ohio State University Wexner Medical Center, James Cancer Hospital and Solove Research Institute, Columbus, OH
| | - Carolyn Presley
- Division of Medical Oncology, Ohio State University Wexner Medical Center, James Cancer Hospital and Solove Research Institute, Columbus, OH
| | - Samuel K Kulp
- Division of Pharmaceutics and Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH
| | - Thomas A Mace
- Division of Medical Oncology, Ohio State University Wexner Medical Center, James Cancer Hospital and Solove Research Institute, Columbus, OH
| | - Christopher C Coss
- Division of Pharmaceutics and Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH
| | - Mitch A Phelps
- Division of Pharmaceutics and Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH.
| | - Dwight H Owen
- Division of Medical Oncology, Ohio State University Wexner Medical Center, James Cancer Hospital and Solove Research Institute, Columbus, OH.
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Cao P, Hong H, Yu Z, Chen G, Qi S. A Novel Clinically Prognostic Stratification Based on Prognostic Nutritional Index Status and Histological Grade in Patients With Gallbladder Cancer After Radical Surgery. Front Nutr 2022; 9:850971. [PMID: 35600830 PMCID: PMC9116425 DOI: 10.3389/fnut.2022.850971] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2022] [Accepted: 04/05/2022] [Indexed: 11/13/2022] Open
Abstract
Purpose Gallbladder carcinoma (GBC) is the most common malignancy of the biliary tract, with a 5-year survival rate of 5%. The prognostic models to predict the prognosis of patients with GBC remain controversial. Therefore, to construct a prognosis prediction of GBC, a retrospective cohort study was carried out to investigate the prognostic nutritional index and histological grade in the long-term outcome of patients with GBC after radical surgery (RS). Methods A retrospective study of a total of 198 patients with GBC who underwent surgical treatment were enrolled. The hematological indicators, imageological data, and perioperative clinical data were acquired for statistical analysis and poor prognosis model construction. Results Prognostic nutrition index (PNI) < 45.88, maximum tumor diameter (MTD) > 2.24 cm, and jaundice (JD) were all associated with a poor prognosis in multivariate logistic regression analysis. The prognosis prediction model was based on the three risk factors, which indicated a superior predictive ability in the primary cohort [area under the curve (AUC) = 0.951] and validation cohort (AUC = 0.888). In multivariate Cox regression analysis, poorly differentiation (PD) was associated with poor 3-year survival. In addition, Kaplan-Meier (KM) survival analysis suggested that GBC patients with high-risk scores and PD had a better prognosis after RS (p < 0.05), but there was no significant difference in prognosis for patients with non-poorly differentiation (NPD) or low-risk scores after RS (p > 0.05). Conclusion Our prediction model for GBC patients with prognosis evaluation is accurate and effective. For patients with PD and high-risk scores, RS is highly recommended; a simple cholecystectomy can also be considered for acceptance for patients with NPD or low-risk score. The significant findings provide a new therapeutic strategy for the clinical treatment of GBC.
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Affiliation(s)
- Peng Cao
- Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China
- Department of Hepatobiliary Surgery and Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital, Fujian Medical University Cancer Center, Fuzhou, China
| | - Haijie Hong
- Department of Hepatobiliary Surgery and Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital, Fujian Medical University Cancer Center, Fuzhou, China
| | - Zijian Yu
- Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China
| | - Guodong Chen
- Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China
| | - Shuo Qi
- Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China
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Yang X, Yin H, Xiao C, Li R, Liu Y. The Prognostic Significance of C-Reactive Protein to Albumin Ratio in Patients With Severe Fever With Thrombocytopenia Syndrome. Front Med (Lausanne) 2022; 9:879982. [PMID: 35572999 PMCID: PMC9099431 DOI: 10.3389/fmed.2022.879982] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Accepted: 04/01/2022] [Indexed: 01/08/2023] Open
Abstract
Background Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with the high case-fatality rate, lacking effective therapies and vaccines. Inflammation-based indexes have been widely used to predict the prognosis of patients with cancers and some inflammatory diseases. In our study, we aim to explore the predictive value of the inflammation-based indexes in SFTS patients. Methods We retrospectively analyzed 82 patients diagnosed with SFTS. The inflammation-based indexes, including neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), aggregate index of systemic inflammation (AISI) and C-reactive protein to albumin ratio (CAR), were compared between the survival and death patients. Receiver operating characteristic (ROC) curves were used to compare the predictive ability of MLR, AISI, and CAR. The survival analysis was based on the Kaplan–Meier (KM) method. Multivariate logistic regression analysis was used to analyze the independent risk factors of poor prognosis in patients with SFTS. Results The CAR is higher in the death group while MLR and AISI were higher in the survival group. The ROC curve analysis indicated CAR exhibited more predictive value than the other indexes and the optimal cut-off value of CAR was equal to or greater than 0.14. KM survival curve showed that higher CAR was significantly correlated to the lower overall survival in SFTS patients. Multivariate logistic regression analysis indicated that CAR was an independent risk factor for poor prognosis in patients with SFTS. Conclusion The CAR is an independent risk factor for death in patients with SFTS and could predict the poor prognosis of SFTS patients. It could be used as a biomarker to help physicians to monitor and treat patients more aggressively to improve clinical prognosis.
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Shijubou N, Sumi T, Yamada Y, Nakata H, Mori Y, Chiba H. Immunological and nutritional predictive factors in patients receiving pembrolizumab for the first-line treatment of non-small cell lung cancer. J Cancer Res Clin Oncol 2022; 148:1893-1901. [DOI: 10.1007/s00432-022-03941-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Accepted: 02/02/2022] [Indexed: 10/18/2022]
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Mojibi Y, Seif F, Mojibi N, Aghamajidi A, Mohsenzadegan M, Torang HA. Efficacy of immunotherapy in obese patients with cancer. Immunopharmacol Immunotoxicol 2022; 44:471-483. [PMID: 35369842 DOI: 10.1080/08923973.2022.2061989] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Obesity is a condition of excessive fat tissue and high body mass index (BMI ≥30), which is increasing worldwide. Excess body weight is associated with poorer results in cancer treatments; however, recent studies emphasized that elevated BMI was associated with improved outcomes in cases treated by immune checkpoint inhibitor (ICI) therapies, which is called the obesity paradox. In this review, we discuss the correlation between obesity and cancer immunotherapy, especially ICIs, the underlying mechanisms, and the outcomes in different types of cancers. In addition, we describe the occurrence of immune-related adverse events (irAE) and the effect of gender in obese patients during immunotherapy using all relevant studies with available full texts.
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Affiliation(s)
- Yasaman Mojibi
- Department of Medical Laboratory Science, Faculty of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran
| | - Farhad Seif
- Department of Immunology and Allergy, Academic Center for Education, Culture, and Research (ACECR), Tehran, Iran.,Neuroscience Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Nastaran Mojibi
- Department of Clinical Biochemistry, Mazandaran University of Medical Sciences, Sari, Iran
| | - Azin Aghamajidi
- Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Monireh Mohsenzadegan
- Department of Medical Laboratory Science, Faculty of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran
| | - Hamzeh-Ali Torang
- Rheumatology Department, Faculty of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran
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Lee J, Choi SH, Baek JH, Baek DW, Kim JG, Kang BW. Clinical Impact of Prognostic Nutrition Index for Advanced Gastric Cancer Patients with Peritoneal Metastases Treated Nivolumab Monotherapy. Chonnam Med J 2022; 58:24-28. [PMID: 35169556 PMCID: PMC8813651 DOI: 10.4068/cmj.2022.58.1.24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2021] [Revised: 11/12/2021] [Accepted: 11/23/2021] [Indexed: 11/06/2022] Open
Abstract
Although nivolumab shows survival benefits for patients with advanced gastric cancer (AGC), predictive biomarkers for nivolumab treatment in AGC remain unclear, especially in the case of peritoneal metastases. This study investigated the clinical significance of the prognostic nutrition index (PNI), reflecting the host nutritional status and immunity, in AGC patients undergoing nivolumab monotherapy. This study retrospectively analyzed 53 AGC patients who received nivolumab between October 2017 and February 2021. Among them, 35 patients with peritoneal metastases were reviewed to investigate the relationship between the PNI and oncological outcomes. The PNI was calculated as 10×serum albumin level (g/dl)+0.005×total lymphocyte count (per mm3) at the first administration of nivolumab. With a median follow-up duration of 2.0 (0.3-13.5) months, the median overall survival (OS) was 2.0 months. The overall response and disease-control rates were 0.0% and 20.0%, respectively. Among the 35 patients, 13 patients were identified as a high-PNI group. In the univariate analysis, the high-PNI group showed a significantly longer PFS and OS than the low-PNI group. In the multivariate analysis, the high-PNI was independently associated with a longer PFS (p=0.021) and OS (p=0.022). The PNI can be useful for predicting PFS and OS in AGC patients with peritoneal metastases. However, further studies are required to validate these results in AGC and new strategies are needed to improve the outcome for AGC patients with peritoneal metastases.
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Affiliation(s)
- Jungmin Lee
- Department of Oncology/Hematology, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Kyungpook National University Cancer Research Institute, Daegu, Korea
| | - Soo Ho Choi
- Department of Internal Medicine, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Jin Ho Baek
- Department of Oncology/Hematology, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Kyungpook National University Cancer Research Institute, Daegu, Korea
| | - Dong Won Baek
- Department of Oncology/Hematology, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Kyungpook National University Cancer Research Institute, Daegu, Korea
| | - Jong Gwang Kim
- Department of Oncology/Hematology, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Kyungpook National University Cancer Research Institute, Daegu, Korea
| | - Byung Woog Kang
- Department of Oncology/Hematology, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Kyungpook National University Cancer Research Institute, Daegu, Korea
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Nutritional Status as a Predictive Biomarker for Immunotherapy Outcomes in Advanced Head and Neck Cancer. Cancers (Basel) 2021; 13:cancers13225772. [PMID: 34830929 PMCID: PMC8616447 DOI: 10.3390/cancers13225772] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Revised: 11/14/2021] [Accepted: 11/16/2021] [Indexed: 02/07/2023] Open
Abstract
The association between pretreatment nutritional status and immunotherapy response in patients with advanced head and neck cancer is unclear. We retrospectively analyzed a cohort of 99 patients who underwent treatment with anti-PD-1 or anti-CTLA-4 antibodies (or both) for stage IV HNSCC between 2014 and 2020 at the Johns Hopkins Hospital. Patient demographics and clinical characteristics were retrieved from electronic medical records. Baseline prognostic nutritional index (PNI) scores and pretreatment body mass index (BMI) trends were calculated. Associations between PNI and BMI were correlated with overall survival (OS), progression-free survival (PFS), and immunotherapy response. In univariate analysis, there was a significant correlation between OS and PFS with baseline PNI (OS: HR: 0.464; 95% CI: 0.265-0.814; PFS: p = 0.007 and HR: 0.525; 95% CI: 0.341-0.808; p = 0.003). Poor OS was also associated with a greater decrease in pretreatment BMI trend (HR: 0.42; 95% CI: 0.229-0.77; p = 0.005). In multivariate analysis, baseline PNI but not BMI trend was significantly associated with OS and PFS (OS: log (HR) = -0.79, CI: -1.6, -0.03, p = 0.041; PFS: log (HR) = -0.78, CI: -1.4, -0.18, p = 0.011). In conclusion, poor pretreatment nutritional status is associated with negative post-immunotherapy outcomes.
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Morimoto K, Yamada T, Yokoi T, Kijima T, Goto Y, Nakao A, Hibino M, Takeda T, Yamaguchi H, Takumi C, Takeshita M, Chihara Y, Yamada T, Hiranuma O, Morimoto Y, Iwasaku M, Kaneko Y, Uchino J, Takayama K. Clinical impact of pembrolizumab combined with chemotherapy in elderly patients with advanced non-small-cell lung cancer. Lung Cancer 2021; 161:26-33. [PMID: 34500218 DOI: 10.1016/j.lungcan.2021.08.015] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Revised: 08/09/2021] [Accepted: 08/26/2021] [Indexed: 10/20/2022]
Abstract
OBJECTIVES Combination therapy of immune checkpoint inhibitors and chemotherapy is considered to be one of the standard treatment options for patients with advanced non-small-cell lung cancer (NSCLC). However, the clinical significance of immune checkpoint inhibitors combined with chemotherapy in elderly patients with NSCLC has not yet been fully understood. Therefore, this study aimed to evaluate how aging affects the therapeutic impact of chemotherapy combine with immune checkpoint inhibitors in elderly patients. MATERIALS AND METHODS We retrospectively analyzed 203 patients with advanced NSCLC who were treated with the combination therapy of pembrolizumab and chemotherapy between January 2019 and December 2019 at 12 institutions in Japan. We analyzed the clinical impacts of age on the following two groups: those who received pembrolizumab with platinum and pemetrexed (pemetrexed regimen) and those who received pembrolizumab with carboplatin and nab-paclitaxel/paclitaxel (paclitaxel regimen). Progression-free and overall survival were assessed via the Kaplan-Meier method. RESULTS Multivariate analysis demonstrated that progression-free and overall survival were significantly shorter in elderly patients (aged ≥75 years) with NSCLC than in non-elderly patients (aged <75 years) with NSCLC in the pemetrexed regimen group. In contrast, there were no significant differences in progression-free and overall survival between elderly patients and non-elderly patients with NSCLC in the paclitaxel regimen group. In elderly patients with NSCLC, a programmed death-ligand 1 tumor proportion score of ≥50% was significantly associated with progression-free survival, and performance status of ≥2 was significantly associated with overall survival. Low albumin level (<3.5 g/dL) was significantly associated with both progression-free and overall survival. CONCLUSION The results of this retrospective study show that the pemetrexed regimen, but not the paclitaxel regimen, was related to poor clinical outcomes in elderly patients with NSCLC.
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Affiliation(s)
- Kenji Morimoto
- Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kajii-cho, Kamigyo-ku, Kyoto, Japan
| | - Tadaaki Yamada
- Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kajii-cho, Kamigyo-ku, Kyoto, Japan.
| | - Takashi Yokoi
- Department of Thoracic Oncology, Hyogo College of Medicine, Hyogo, Japan
| | - Takashi Kijima
- Department of Thoracic Oncology, Hyogo College of Medicine, Hyogo, Japan
| | - Yasuhiro Goto
- Department of Respiratory Medicine, Fujita Health University, Aichi, Japan
| | - Akira Nakao
- Department of Respiratory Medicine, Faculty of Medicine, Fukuoka University, Fukuoka, Japan
| | - Makoto Hibino
- Department of Respiratory Medicine, Shonan Fujisawa Tokushukai Hospital, Kanagawa, Japan
| | - Takayuki Takeda
- Department of Respiratory Medicine, Japanese Red Cross Kyoto Daini Hospital, Kyoto, Japan
| | - Hiroyuki Yamaguchi
- Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Chieko Takumi
- Department of Respiratory Medicine, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan
| | - Masafumi Takeshita
- Department of Respiratory Medicine, Ichinomiyanishi Hospital, Aichi, Japan
| | - Yusuke Chihara
- Department of Respiratory Medicine, Uji-Tokushukai Medical Center, Kyoto, Japan
| | - Takahiro Yamada
- Department of Pulmonary Medicine, Matsushita Memorial Hospital, Osaka, Japan
| | - Osamu Hiranuma
- Department of Pulmonary Medicine, Otsu City Hospital, Shiga, Japan
| | - Yoshie Morimoto
- Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kajii-cho, Kamigyo-ku, Kyoto, Japan
| | - Masahiro Iwasaku
- Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kajii-cho, Kamigyo-ku, Kyoto, Japan
| | - Yoshiko Kaneko
- Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kajii-cho, Kamigyo-ku, Kyoto, Japan
| | - Junji Uchino
- Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kajii-cho, Kamigyo-ku, Kyoto, Japan
| | - Koichi Takayama
- Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kajii-cho, Kamigyo-ku, Kyoto, Japan
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