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Nakazawa N, Sohda M, Hosoi N, Watanabe T, Kumakura Y, Yamashita T, Tanaka N, Saito K, Kimura A, Kasuga K, Nakazato K, Yoshinari D, Shimizu H, Ubukata Y, Hosaka H, Sano A, Sakai M, Ogawa H, Shirabe K, Saeki H. Conversion Surgery After Chemotherapy Plus Nivolumab as the First-Line Treatment for Unresectable Advanced or Recurrent Gastric Cancer and a Biomarker Study Using the Gustave Roussy Immune Score: A Multicenter Study. Ann Surg Oncol 2024; 31:9023-9029. [PMID: 39225857 DOI: 10.1245/s10434-024-16161-4] [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: 06/03/2024] [Accepted: 08/24/2024] [Indexed: 09/04/2024]
Abstract
BACKGROUND There are few reports on conversion surgery (CS) after chemotherapy plus nivolumab as a first-line treatment in patients with unresectable advanced or recurrent gastric cancer (GC). This multicenter study was conducted to analyze real-world data on CS after chemotherapy plus nivolumab as a first-line treatment and to identify predictive biomarkers. METHODS This multicenter study included 104 patients who received chemotherapy plus nivolumab as primary treatment for unresectable advanced recurrent GC from 12 institutes. We investigated and analyzed patient characteristics and blood test data in the presence or absence of CS, the relationship between the Gustave Roussy Immune Score (GRIm-s) and CS, and the characteristics of CS cases. RESULTS CS was performed in 12 patients (11.5%). Eastern Cooperative Oncology Group Performance Status (ECOG-PS) was significantly better in patients who underwent CS (p < 0.0001). There were no CS cases with high-risk GRIm-s (0%), however there were 22 non-CS cases (23.9%). No high-risk GRIm-s cases were converted to CS. Minimally invasive surgery was performed in 50.0% of the cases, with R0 resection in all cases and only one case of urinary retention (Grade II) as a postoperative complication, indicating a good postoperative short-term outcome. There were two cases of postoperative recurrence (16.7%), both of which were grade 1b. CONCLUSIONS The short-term postoperative results of CS after chemotherapy plus nivolumab as the first-line treatment for GC were acceptable in this study. There were no high-risk GRIm-s cases among those who underwent CS, suggesting that the GRIm-s may be a predictor of CS.
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Affiliation(s)
- Nobuhiro Nakazawa
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Gunma, 371-8511, Japan.
| | - Makoto Sohda
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Gunma, 371-8511, Japan
| | - Nobuhiro Hosoi
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Gunma, 371-8511, Japan
| | - Takayoshi Watanabe
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Gunma, 371-8511, Japan
| | - Yuji Kumakura
- Department of Surgery, Tonechuo Hospital, Numata, Gunma, Japan
| | - Toshiki Yamashita
- Department of Surgery, Subaru Health Insurance Society Ota Memorial Hospital, Ota, Gunma, Japan
| | - Naritaka Tanaka
- Department of Surgery, Japanese Red Cross Haramachi Hospital, Agatsumagun, Gunma, Japan
| | - Kana Saito
- Department of Surgery, Japan Community Healthcare Organization Gunma Central Hospital, Maebashi, Gunma, Japan
| | - Akiharu Kimura
- Department of Surgery, Kiryu Kosei General Hospital, Kiryu, Gunma, Japan
| | - Kengo Kasuga
- Department of Gastroenterology, Isesaki Municipal Hospital, Isesaki, Gunma, Japan
| | - Kenji Nakazato
- Department of Surgery, Fujioka General Hospital, Fujioka, Gunma, Japan
| | - Daisuke Yoshinari
- Department of Surgery, National Hospital Organization Shibukawa Medical Center, Shibukawa, Gunma, Japan
| | - Hisashi Shimizu
- Department of Surgery, Japanese Red Cross Maebashi Hospital, Maebashi, Gunma, Japan
| | - Yasunari Ubukata
- Department of Surgery, National Hospital Organization Takasaki General Medical Center, Takasaki, Gunma, Japan
| | - Hisashi Hosaka
- Department of Gastroenterology, Gunma Prefectural Cancer Center, Ohta, Gunma, Japan
| | - Akihiko Sano
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Gunma, 371-8511, Japan
| | - Makoto Sakai
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Gunma, 371-8511, Japan
| | - Hiroomi Ogawa
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Gunma, 371-8511, Japan
| | - Ken Shirabe
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Gunma, 371-8511, Japan
| | - Hiroshi Saeki
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Gunma, 371-8511, Japan
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Tan C, Xu J, Yang X, Wu D, Zhang S, Liu S, Yu B, Huang Y. The Gustave Roussy Immune score (GRIm score) as a novel prognostic score for early breast cancer patients: A real-world retrospective study. Int J Med Sci 2024; 21:2640-2654. [PMID: 39512692 PMCID: PMC11539385 DOI: 10.7150/ijms.99724] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Accepted: 10/02/2024] [Indexed: 11/15/2024] Open
Abstract
Background and objective: The aim of this research is to investigate whether the GRIm score serves as a novel prognostic tool for predicting the survival rates among early breast cancer patients undergoing surgical treatment. Methods: This retrospective study included 313 cases of breast cancer patients hospitalized in our hospital from January 2015 to November 2015. All enrolled patients received surgery and had no metastasis. The GRIm score was based on five objective markers: (1) albumin level (<3.5 g/L = 1 point), (2) LDH level (≥245 U/L = 1 point); (3) AST-to-ALT ratio (≥1.44 = 1 point); (4) total bilirubin level (≥21 μmol/ml = 1 point); (5) NLR (≥1.51 = 1 point). The best critical value was 1.51 for NLR by ROC. Patients were categorized into two groups based on GRIm scores: low-score group (0 point) and high-score group (1 to 5 points). Kaplan-Meier method and log rank test were utilized to estimate disease free survival (DFS) and overall survival (OS). Both univariate analysis and multivariate Cox analysis were used to analyze the relationship among the enrolled parameters. Nomograms were formulated reliant on the outcomes of multivariate Cox analysis. Results: Based on the GRIm score, the cohort was divided into two groups: a low-score group with 81 cases and a high-score group with 232 cases. The mean DFS and OS were significantly prolonged in low-score group compared to high-score group (DFS: 74.39 vs. 66.20 months, χ2=8.729, P=0.0031; OS: 83.71 vs. 76.40 months, χ2=8.729, P=0.0031). According to multivariable analysis, GRIm score was notably correlated with DFS (HR: 2.789, 95% CI: 1.304-5.965, P= 0.004) and OS (HR: 3.015, 95% CI: 1.409-10.087, P=0.004). Nomograms exhibited excellent predictive performance for DFS (C-index: 0.823) and OS (C-index: 0.807). Conclusions: GRIm score serves as a predictive tool for assessing the prognosis of early breast cancer patients. Nomograms based on GRIm score show good prediction ability.
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Affiliation(s)
- Chunlei Tan
- Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, P.R. China
| | - Jinling Xu
- Endoscope Department, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, P.R. China
| | - Xiaotian Yang
- Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, P.R. China
| | - Danping Wu
- Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, P.R. China
| | - Shiyuan Zhang
- Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, P.R. China
| | - Shuqiang Liu
- Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, P.R. China
| | - Boqian Yu
- Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, P.R. China
| | - Yuanxi Huang
- Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, P.R. China
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Nakazawa N, Sohda M, Endo M, Hosoi N, Uchida S, Watanabe T, Sano A, Sakai M, Ogawa H, Shirabe K, Saeki H. The Gustave Roussy Immune score is a powerful biomarker for predicting therapeutic resistance to chemotherapy in gastric cancer patients. Cancer Chemother Pharmacol 2024; 94:517-522. [PMID: 39060627 DOI: 10.1007/s00280-024-04692-2] [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: 11/21/2023] [Accepted: 06/17/2024] [Indexed: 07/28/2024]
Abstract
PURPOSE It is highly important to be able to predict the therapeutic efficacy of chemotherapy on patients with unresectable advanced or recurrent gastric cancer (GC). The Gustave Roussy Immune Score (GRIm-s) is a predictor of therapeutic sensitivity to chemotherapy and immune checkpoint inhibitors (ICIs) in other cancers. The present study aimed to analyze the association of the GRIm-s with the therapeutic sensitivity of first-line chemotherapy in GC patients. METHODS We included 156 patients receiving primary chemotherapy treatment for unresectable or advanced recurrent GC between January 2012 and December 2021 at our institution. We evaluated the correlation between the GRIm-s and therapeutic sensitivities to chemotherapy. The GRIm-s was assessed before the start of first-line chemotherapy. RESULTS Among the 156 patients, 138 (88.5%) and 18 (11.5%) were classified in the low- and high-risk groups, respectively. The GRIm-s high-risk group was significantly older (p = 0.013), had more advanced unresectable cancer (p = 0.0098), and was significantly less likely to progress to second-line chemotherapy (p = 0.014). The overall survival rate (OS) (p = 0.039) and the progression free survival rate (PFS) (p = 0.017) were significantly worse in the GRIm-s high-risk group. The high GRIm-s was an independent prognostic factor for poor survival in multivariate analysis (p = 0.0094). CONCLUSIONS Focusing on the GRIm-s before first-line chemotherapy initiation for unresectable advanced or postoperative recurrent GC was useful in predicting the therapeutic resistance to chemotherapy, transition to second-line chemotherapy, and poor prognosis.
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Affiliation(s)
- Nobuhiro Nakazawa
- Department of General Surgical Science, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, 371-8511, Japan
| | - Makoto Sohda
- Department of General Surgical Science, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, 371-8511, Japan.
| | - Mizuki Endo
- Department of General Surgical Science, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, 371-8511, Japan
| | - Nobuhiro Hosoi
- Department of General Surgical Science, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, 371-8511, Japan
| | - Shintaro Uchida
- Department of General Surgical Science, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, 371-8511, Japan
| | - Takayoshi Watanabe
- Department of General Surgical Science, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, 371-8511, Japan
| | - Akihiko Sano
- Department of General Surgical Science, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, 371-8511, Japan
| | - Makoto Sakai
- Department of General Surgical Science, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, 371-8511, Japan
| | - Hiroomi Ogawa
- Department of General Surgical Science, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, 371-8511, Japan
| | - Ken Shirabe
- Department of General Surgical Science, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, 371-8511, Japan
| | - Hiroshi Saeki
- Department of General Surgical Science, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, 371-8511, Japan
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Mazzella A, Orlandi R, Maiorca S, Uslenghi C, Chiari M, Bertolaccini L, Casiraghi M, Lo Iacono G, Girelli L, Spaggiari L. How General and Inflammatory Status Impacts on the Prognosis of Patients Affected by Lung Cancer: State of the Art. Biomedicines 2024; 12:1554. [PMID: 39062127 PMCID: PMC11274951 DOI: 10.3390/biomedicines12071554] [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: 04/16/2024] [Revised: 06/23/2024] [Accepted: 07/09/2024] [Indexed: 07/28/2024] Open
Abstract
Pulmonary cancer is often associated with systemic inflammation and poor nutritional status and these two aspects are strongly correlated and related to the scarce infiltration of a tumor by immune cells. We reviewed all English literature reviews from 2000 to 2024 from PubMed, Scopus and Google Scholar, including original articles, review articles, and metanalyses. We excluded non-English language articles and case reports/case series. Generally speaking, nutritional and inflammatory status largely affect medium and long-term prognosis in lung cancer patients. A correct stratification of patients could improve their preoperative general functional nutritional and inflammatory status, minimizing, therefore, possible treatment complications and improving long-term prognosis.
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Affiliation(s)
- Antonio Mazzella
- Division of Thoracic Surgery, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy; (R.O.); (S.M.); (C.U.); (M.C.); (L.B.); (M.C.); (G.L.I.); (L.G.); (L.S.)
| | - Riccardo Orlandi
- Division of Thoracic Surgery, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy; (R.O.); (S.M.); (C.U.); (M.C.); (L.B.); (M.C.); (G.L.I.); (L.G.); (L.S.)
| | - Sebastiano Maiorca
- Division of Thoracic Surgery, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy; (R.O.); (S.M.); (C.U.); (M.C.); (L.B.); (M.C.); (G.L.I.); (L.G.); (L.S.)
| | - Clarissa Uslenghi
- Division of Thoracic Surgery, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy; (R.O.); (S.M.); (C.U.); (M.C.); (L.B.); (M.C.); (G.L.I.); (L.G.); (L.S.)
| | - Matteo Chiari
- Division of Thoracic Surgery, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy; (R.O.); (S.M.); (C.U.); (M.C.); (L.B.); (M.C.); (G.L.I.); (L.G.); (L.S.)
| | - Luca Bertolaccini
- Division of Thoracic Surgery, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy; (R.O.); (S.M.); (C.U.); (M.C.); (L.B.); (M.C.); (G.L.I.); (L.G.); (L.S.)
| | - Monica Casiraghi
- Division of Thoracic Surgery, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy; (R.O.); (S.M.); (C.U.); (M.C.); (L.B.); (M.C.); (G.L.I.); (L.G.); (L.S.)
| | - Giorgio Lo Iacono
- Division of Thoracic Surgery, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy; (R.O.); (S.M.); (C.U.); (M.C.); (L.B.); (M.C.); (G.L.I.); (L.G.); (L.S.)
| | - Lara Girelli
- Division of Thoracic Surgery, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy; (R.O.); (S.M.); (C.U.); (M.C.); (L.B.); (M.C.); (G.L.I.); (L.G.); (L.S.)
| | - Lorenzo Spaggiari
- Division of Thoracic Surgery, IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy; (R.O.); (S.M.); (C.U.); (M.C.); (L.B.); (M.C.); (G.L.I.); (L.G.); (L.S.)
- Division of Oncology and Hemato-Oncology, University of Milan, 20141 Milan, Italy
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Takenaka Y, Takemoto N, Otsuka T, Nishio M, Tanida M, Fujii T, Hayashi K, Suzuki M, Mori M, Yamamoto Y, Uno A, Inohara H. Validation and comparison of prognostic scoring systems in patients with head and neck squamous cell carcinoma treated with nivolumab. Jpn J Clin Oncol 2024; 54:761-769. [PMID: 38555496 DOI: 10.1093/jjco/hyae042] [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: 01/06/2024] [Accepted: 03/13/2024] [Indexed: 04/02/2024] Open
Abstract
OBJECTIVE Several scoring systems have been developed to predict prognosis in patients with refractory cancer. We aimed to validate eight scoring systems and determine the best method for predicting the prognosis of head and neck squamous cell carcinoma treated with nivolumab. METHODS This multicentre retrospective study involved 154 patients with recurrent and/or metastatic head and neck squamous cell carcinoma treated with nivolumab between 2017 and 2020. Oncological outcomes were assessed according to the scoring systems, including MD Anderson Cancer Center + neutrophil-to-lymphocyte ratio and Hammersmith scores. Objective response, overall survival and progression-free survival were evaluated using logistic regression and Cox proportional hazards analyses. Receiver operating curve analysis was used to calculate the area under the curve and estimate the efficacy of each score. RESULTS No significant associations were found between the responses and any score. Seven of the eight scoring systems were associated with disease control (odds ratio, 0.26-0.70). Amongst the eight scoring systems, MD Anderson Cancer Center + neutrophil-to-lymphocyte ratio showed the highest area under the curve for predicting response and disease control. Seven scoring systems were prognostic factors for progression-free survival (hazard ratio, 1.22-1.95). All eight scoring systems were prognostic factors for overall survival (hazard ratio, 1.62-3.83). According to the time-dependent receiver operating characteristics analysis for overall survival, the Hammersmith scoring system had the best predictive ability at 3 months, and the MD Anderson Cancer Center + neutrophil-to-lymphocyte ratio scoring system had the highest area under the curve between 6 and 24 months. CONCLUSIONS MD Anderson Cancer Center + neutrophil-to-lymphocyte ratio and Hammersmith scoring systems were better predictors of prognosis in patients with head and neck squamous cell carcinoma treated with nivolumab.
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Affiliation(s)
- Yukinori Takenaka
- Department of Otorhinolaryngology-Head and Neck Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Norihiko Takemoto
- Department of Otorhinolaryngology-Head and Neck Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Tomoyuki Otsuka
- Department of Medical Oncology, International Cancer Institute, Osaka, Japan
| | - Minako Nishio
- Department of Medical Oncology, International Cancer Institute, Osaka, Japan
| | - Masashi Tanida
- Department of Head and Neck Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Takashi Fujii
- Department of Head and Neck Surgery, Osaka International Cancer Institute, Osaka, Japan
| | - Kazuki Hayashi
- Department of Otorhinolaryngology-Head and Neck Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Motoyuki Suzuki
- Department of Otorhinolaryngology-Head and Neck Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Masashi Mori
- Department of Otorhinolaryngology-Head and Neck Surgery, General Medical Center, Osaka, Japan
| | - Yoshifumi Yamamoto
- Department of Otorhinolaryngology-Head and Neck Surgery, General Medical Center, Osaka, Japan
| | - Atsuhiko Uno
- Department of Otorhinolaryngology-Head and Neck Surgery, General Medical Center, Osaka, Japan
| | - Hidenori Inohara
- Department of Otorhinolaryngology-Head and Neck Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
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Ji Y, Wang W. Prognostic Value of the Gustave Roussy Immune Score in Lung Cancer: A Meta-Analysis. Nutr Cancer 2024; 76:707-716. [PMID: 38841900 DOI: 10.1080/01635581.2024.2361508] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2024] [Revised: 05/23/2024] [Accepted: 05/24/2024] [Indexed: 06/07/2024]
Abstract
PURPOSE To clarify the prognostic role of the Gustave Roussy immune (GRIm) score in lung cancer. METHODS The PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases were searched up to March 30, 2024. The primary outcomes included overall survival (OS) and progression-free survival (PFS). Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to evaluate the associations between the GRIm score and survival, and subgroup analyses were performed based on pathological type (non-small cell lung cancer vs. small cell lung cancer), tumor stage (advanced vs. limited stage) and treatment approach (immune checkpoint inhibitor vs. surgery vs. chemotherapy). RESULTS Eight studies with 1,333 participants were included. The pooled results showed that a higher GRIm score predicted worse OS (HR = 1.96, 95% CI: 1.54-2.49, P < 0.001) and PFS (HR = 1.64, 95% CI: 1.22-2.21, P = 0.001). Subgroup analyses for OS and PFS showed similar results. However, subgroup analyses for PFS indicated that the association between the GRIm score and PFS was nonsignificant among patients with small cell lung cancer (P = 0.114) and among patients treated with chemotherapy (P = 0.276). CONCLUSION The GRIm score might serve as a novel prognostic factor for lung cancer. Additional studies are still needed to verify these findings.
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Affiliation(s)
- Yanli Ji
- Department of Thoracic Surgery, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu, China
| | - Wenping Wang
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China
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Sahin TK, Rizzo A, Aksoy S, Guven DC. Prognostic Significance of the Royal Marsden Hospital (RMH) Score in Patients with Cancer: A Systematic Review and Meta-Analysis. Cancers (Basel) 2024; 16:1835. [PMID: 38791914 PMCID: PMC11120545 DOI: 10.3390/cancers16101835] [Citation(s) in RCA: 20] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2024] [Revised: 04/29/2024] [Accepted: 05/09/2024] [Indexed: 05/26/2024] Open
Abstract
BACKGROUND Cancer remains a leading cause of death globally, necessitating the identification of prognostic biomarkers to guide treatment decisions. The Royal Marsden Hospital (RMH) score, based on readily available blood tests and clinical features, has emerged as a prognostic tool, although its performance across variable clinical scenarios is not thoroughly delineated. Therefore, we aimed to systematically assess the association between RMH score and survival in cancer patients. METHODS We conducted a systematic literature search across Pubmed, Scopus, and Web of Science databases for studies published up to 15 February 2024. We performed a meta-analysis with the generic inverse variance method with a random-effects model and reported hazard ratios (HR) with 95% confidence intervals (CI). RESULTS Nineteen studies encompassing 127,230 patients were included. A higher RMH score was significantly associated with worse overall survival (OS) (HR: 2.09, 95% CI: 1.87-2.33, p < 0.001) and progression-free survival (PFS) (HR: 1.80, 95% CI: 1.48-2.18, p < 0.001). This association was consistent across various subgroups, including study population (clinical trial vs. real-world cohort), geographic region, and tumor type. CONCLUSION This meta-analysis, including over a hundred thousand patients, demonstrates a negative association between a higher RMH score and survival in cancer patients. The RMH score holds promise as a readily available prognostic tool across diverse cancer types and clinical settings. Future research should focus on validating and refining this score to aid clinical decision-making.
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Affiliation(s)
- Taha Koray Sahin
- Department of Medical Oncology, Hacettepe University, Ankara 06100, Turkey; (T.K.S.); (S.A.)
| | | | - Sercan Aksoy
- Department of Medical Oncology, Hacettepe University, Ankara 06100, Turkey; (T.K.S.); (S.A.)
| | - Deniz Can Guven
- Medical Oncology Clinic, Health Sciences University, Elazig City Hospital, Elazig 23280, Turkey
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Stares M, Brown LR, Abhi D, Phillips I. Prognostic Biomarkers of Systemic Inflammation in Non-Small Cell Lung Cancer: A Narrative Review of Challenges and Opportunities. Cancers (Basel) 2024; 16:1508. [PMID: 38672590 PMCID: PMC11048253 DOI: 10.3390/cancers16081508] [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: 03/04/2024] [Revised: 04/03/2024] [Accepted: 04/08/2024] [Indexed: 04/28/2024] Open
Abstract
Non-small cell lung cancer (NSCLC) is a common malignancy and is associated with poor survival outcomes. Biomarkers of systemic inflammation derived from blood tests collected as part of routine clinical care offer prognostic information for patients with NSCLC that may assist clinical decision making. They are an attractive tool, as they are inexpensive, easily measured, and reproducible in a variety of healthcare settings. Despite the wealth of evidence available to support them, these inflammatory biomarkers are not yet routinely used in clinical practice. In this narrative review, the key inflammatory indices reported in the literature and their prognostic significance in NSCLC are described. Key challenges limiting their clinical application are highlighted, including the need to define the optimal biomarker of systemic inflammation, a lack of understanding of the systemic inflammatory landscape of NSCLC as a heterogenous disease, and the lack of clinical relevance in reported outcomes. These challenges may be overcome with standardised recording and reporting of inflammatory biomarkers, clinicopathological factors, and survival outcomes. This will require a collaborative approach, to which this field of research lends itself. This work may be aided by the rise of data-driven research, including the potential to utilise modern electronic patient records and advanced data-analysis techniques.
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Affiliation(s)
- Mark Stares
- Edinburgh Cancer Centre, NHS Lothian, Edinburgh EH4 2XU, UK
- Cancer Research UK Scotland Centre, University of Edinburgh, Edinburgh EH4 2XR, UK
| | - Leo R. Brown
- Cancer Research UK Scotland Centre, University of Edinburgh, Edinburgh EH4 2XR, UK
| | - Dhruv Abhi
- Edinburgh Cancer Centre, NHS Lothian, Edinburgh EH4 2XU, UK
| | - Iain Phillips
- Edinburgh Cancer Centre, NHS Lothian, Edinburgh EH4 2XU, UK
- Cancer Research UK Scotland Centre, University of Edinburgh, Edinburgh EH4 2XR, UK
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Jiang H, Li B, Wu M, Wang Q, Li Y. Association of the Advanced Lung Cancer Inflammation Index (ALI) and Gustave Roussy Immune (GRIm) score with immune checkpoint inhibitor efficacy in patients with gastrointestinal and lung cancer. BMC Cancer 2024; 24:428. [PMID: 38589844 PMCID: PMC11000368 DOI: 10.1186/s12885-024-12149-1] [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: 11/29/2023] [Accepted: 03/20/2024] [Indexed: 04/10/2024] Open
Abstract
OBJECTIVE This study aimed to conduct a comprehensive analysis, evaluating the prognostic significance of the baseline Advanced Lung Cancer Inflammation Index (ALI) and Gustave Roussy Immune (GRIm) Score in patients undergoing immune checkpoint inhibitor (ICI) therapy. METHODS A comprehensive search was performed across various databases, including PubMed, the Cochrane Library, EMBASE, and Google Scholar, until October 21, 2023, to compile relevant articles for analysis. The investigation encompassed diverse clinical outcomes, including overall survival (OS) and progression-free survival (PFS). RESULTS This analysis included a total of 15 articles, comprising 19 studies involving 3335 patients. Among the 19 studies, nine studies focused on NSCLC, and six studies were conducted on HCC. Pooled results revealed that patients with elevated ALI levels experienced prolonged OS (HR: 0.51, 95% CI: 0.37-0.70, p < 0.001) and extended PFS (HR: 0.61, 95% CI: 0.52-0.72, p < 0.001). Furthermore, a GRIm score > 1 was associated with reduced OS (HR: 2.07, 95% CI: 1.47-2.92, p < 0.001) and diminished PFS (HR: 1.78, 95% CI: 1.35-2.34, p < 0.001) in cancer patients receiving ICIs. Subgroup analysis indicated that ALI cutoff values of 18 exhibited enhanced predictive potential. Additionally, for HCC patients, those with HCC-GRIm score > 2 showed a substantially decreased risk of mortality compared to individuals with HCC-GRIm score ≤ 2 (HR: 2.63, 95% CI: 1.89-3.65, p < 0.001). CONCLUSION The ALI and GRIm score served as dependable prognostic indicators for patients undergoing ICI therapy in the context of cancer treatment.
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Affiliation(s)
- Hao Jiang
- Department of General Surgery, Taizhou Central Hospital (Taizhou University, Hospital), Taizhou, China
| | - Borui Li
- Department of Urologic Surgery, Cancer Hospital of China Medical University (Liaoning Cancer Hospital & Institute), Shenyang, China
| | - Min Wu
- Department of Oncology, The Third People's Hospital of Honghe Prefecture, Gejiu, China
| | - Qimei Wang
- Hunan Academy of Traditional Chinese Medicine, Changsha, China.
| | - Yijin Li
- Department of Colorectal and Anorectal Surgery, Hunan Hospital of Integrated Tradmonal Chinese and Western Medicine (Hunan Academy of Traditional Chinese Medicine Affiliated Hospital), Changsha, China.
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Cotan H, Iaciu C, Radu E, Niculae T, Rosu OA, Nitipir C. Gustave Roussy Immune Score (GRIm-Score) as a Prognostic and Predictive Score in Metastatic Colorectal Cancer. Cureus 2024; 16:e58935. [PMID: 38800241 PMCID: PMC11116742 DOI: 10.7759/cureus.58935] [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] [Accepted: 04/24/2024] [Indexed: 05/29/2024] Open
Abstract
INTRODUCTION Metastatic colorectal cancer (mCRC) presents significant clinical challenges due to its heterogeneous nature and variable treatment responses. The Gustave Roussy Immune Score (GRIm-Score) has emerged as a potential biomarker for prognostication and prediction in mCRC, although its precise role remains under investigation. METHODS We conducted a retrospective study that included 173 patients diagnosed with mCRC. The patients were treated in the first line with 5-fluorouracil (5-FU)-based chemotherapy (CHT) and a molecular agent based on their eligibility. We assessed the overall survival (OS) time, progression-free survival (PFS) time, and the overall response rate (ORR), utilizing the GRIm-score measured at baseline (referred to as GRImT0) and the variance between GRImT0 and the GRIm score measured three months after treatment initiation (referred to as GRIm∆). We also performed a subgroup analysis based on the type of treatment received. RESULTS Our analysis revealed that the GRIm-Score holds promise as a prognostic marker in mCRC, with high scores correlating with poorer survival outcomes. However, in the subgroup analysis, this prognostic value remained relevant only for patients treated with CHT and anti-EGFR (epidermal growth factor receptor) agents, such as cetuximab and panitumumab. GRIm-Score exhibited no predictive value irrespective of the treatment received. CONCLUSION The GRIm-Score shows potential as a prognostic mCRC, although we believe that this potential is limited. Integration of the GRIm-Score into clinical practice should be done with caution and is not recommended at this time. However, further research is needed to fully elucidate its clinical utility and optimize its incorporation into routine clinical care.
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Affiliation(s)
- Horia Cotan
- Oncology, Carol Davila University of Medicine and Pharmacy, Bucharest, ROU
| | - Cristian Iaciu
- Oncology, Carol Davila University of Medicine and Pharmacy, Bucharest, ROU
| | - Emilescu Radu
- Gastroenterology, Carol Davila University of Medicine and Pharmacy, Bucharest, ROU
| | - Tudor Niculae
- Nephrology, Nephrology Hospital Dr. Carol Davila, Bucharest, ROU
| | - Oana A Rosu
- Oncology, Elias Emergency University Hospital, Bucharest, ROU
| | - Cornelia Nitipir
- Oncology, Carol Davila University of Medicine and Pharmacy, Bucharest, ROU
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11
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Sun KX, Xu RQ, Rong H, Pang HY, Xiang TX. Prognostic significance of the Gustave Roussy immune (GRIm) score in cancer patients: a meta-analysis. Ann Med 2023; 55:2236640. [PMID: 37851510 PMCID: PMC10586078 DOI: 10.1080/07853890.2023.2236640] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Accepted: 07/07/2023] [Indexed: 10/20/2023] Open
Abstract
BACKGROUND The prognostic value of the Gustave Roussy immune (GRIm) score in cancer patients has been widely reported but remains inconsistent. The aim of this study is to systematically investigate the relationship between the GRIm score and survival outcomes in cancer patients. METHODS Relevant literature was identified using electronic databases including Web of Science, PubMed, and Embase from the inception to March 2023. The primary endpoints were long-term oncological outcomes. Subgroup analysis and sensitivity analysis were conducted during the meta-analysis. RESULTS Fifteen studies (20 cohorts) including 4997 cancer patients were enrolled. The combined results revealed that patients in the high GRIm group had a deteriorated overall survival (HR = 2.07 95%CI: 1.73-2.48; p < 0.0001; I2 = 62%) and progression-free survival (HR = 1.42; 95%CI: 1.22-1.66; p < 0.0001; I2 = 36%). The prognostic values of GRIm on overall survival and progression-free survival were observed across various tumour types and tumour stages. Sensitivity analysis supported the stability and reliability of the above results. CONCLUSION Our evidence suggested that the GRIm score could be a valuable prognostic marker in cancer patients, which can be used by clinicians to stratify patients and formulate individualized treatment plans.
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Affiliation(s)
- Ke-Xin Sun
- Department of Oncology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Ru-Qin Xu
- Department of Oncology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Huan Rong
- Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing, China
| | - Hua-Yang Pang
- Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing, China
| | - Ting-Xiu Xiang
- Department of Oncology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing, China
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12
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Yu X, Yang R, He Z, Li K, Zeng P. Construction and validation of a nomogram for hepatocellular carcinoma patients based on HCC-GRIm score. J Cancer Res Clin Oncol 2023; 149:12013-12024. [PMID: 37421461 DOI: 10.1007/s00432-023-05037-x] [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: 05/10/2023] [Accepted: 06/28/2023] [Indexed: 07/10/2023]
Abstract
PURPOSE To construct a nomogram for hepatocellular carcinoma (HCC) patients base on HCC-GRIm score. METHODS Clinical cases of HCC patients diagnosed at Hunan Integrated Traditional Chinese and Western Medicine Hospital were included, and these were randomly divided into the training cohort (n = 219) and the validation cohort (n = 94), and those patients were divided into low GRIm-Score group (scores 0, 1, and 2) and high GRIm-Score group (scores 3, 4, and 5). In the training cohort, independent risk factors were determined by Cox regression analysis, and a nomogram was constructed by independent risk factors. The efficiency and the clinical applicability of nomograms were evaluated using ROC curves, calibration plot, and the decision curve (DCA), and the patients were divided into high-risk, middle-risk, and low-risk groups according to total score of nomogram. RESULTS Compared to low HCC-GRIm score group, high HCC-GRIm score group with BCLC stage is more advanced (P < 0.001), and fewer patients received TACE (P = 0.005) and surgical treatment (P = 0.001). There was higher rate of the presence of vascular invasion (P < 0.001) and distant metastasis (P < 0.001). Multivariate Cox regression analysis screened 4 independent risk factors to construct a nomogram of HCC patients, including HCC-GRIm score, BCLC stage, albumin-to-globulin ratio (AGR), and glutamyl trans-peptidase (GGT). The consistency index (C-index) of the nomogram of the training was 0.843 (0.832-0.854) and the validation was 0.870 (0.856-0.885). The time-dependent parameter showed the AUC values of the training cohort at 1, 3, and 5 years were 0.954 (95% CI 0.929-0.980), 0.952 (95% CI 0.919-0.985), and 925 (95% CI 0.871-0.979), while the AUC values of validation cohort at 1, 3, and 5 years were 0.974 (95% CI 0.950-0.998), 0.965 (95% CI 0.931-0.999), and 0.959 (95% CI 0.898-1.021). The calibration plot showed the nomogram fits well onto perfect curves, and the DCA curve showed the net benefit of the nomogram at a certain probability threshold is significantly higher than the net benefit of the BCLC stage at the same threshold probability. Finally, all patients were divided into high-risk, middle-risk, and low-risk groups based on the total score of nomogram, and it showed effectively to identify high-risk patients. CONCLUSION The nomogram constructed by the independent risk factors can predict the prognosis of HCC patients, providing an effective tool with clinical workers to evaluate the prognosis and survival time of HCC patients.
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Affiliation(s)
- Xiaopeng Yu
- Hunan University of Chinese Medicine, Changsha, 410208, Hunan, China
| | - Renyi Yang
- Hunan University of Chinese Medicine, Changsha, 410208, Hunan, China
| | - Zuomei He
- Hunan Academy of Traditional Chinese Medicine Affiliated Hospital, Changsha, 410006, Hunan, China
| | - Kexiong Li
- Hunan Academy of Traditional Chinese Medicine Affiliated Hospital, Changsha, 410006, Hunan, China.
- Cancer Research Institute of Hunan Academy of Traditional Chinese Medicine, Changsha, 410006, Hunan, China.
| | - Puhua Zeng
- Hunan Academy of Traditional Chinese Medicine Affiliated Hospital, Changsha, 410006, Hunan, China.
- Cancer Research Institute of Hunan Academy of Traditional Chinese Medicine, Changsha, 410006, Hunan, China.
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Shi Y, Shen G, Zeng Y, Ju M, Chen X, He C, Liang L, Ge X, Sun X, Di X. Predictive values of the hemoglobin, albumin, lymphocyte and platelet score (HALP) and the modified -Gustave Roussy immune score for esophageal squamous cell carcinoma patients undergoing concurrent chemoradiotherapy. Int Immunopharmacol 2023; 123:110773. [PMID: 37562292 DOI: 10.1016/j.intimp.2023.110773] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Revised: 07/06/2023] [Accepted: 08/04/2023] [Indexed: 08/12/2023]
Abstract
The hemoglobin, albumin, lymphocyte and platelet (HALP) score and the Gustave Roussy immune score (GRIm⁃Score) are prognostic markers in several types of malignant tumors. The prognostic values of HALP score and GRIm⁃Score in concurrent chemoradiotherapy for unresectable esophageal cancer remain unknown. METHODS We enrolled 150 esophageal squamous cell carcinoma (ESCC) patients who underwent concurrent chemoradiotherapy in our institution between 2013 and 2018. The cutoff values for HALP, and GRIm⁃Score were defined by using receiver's operating characteristic curves. Survival was analyzed with the Kaplan- Meier method, with differences analyzed with the log-rank test. Multivariate Cox proportional-hazards models were used to evaluate the prognostic significance of HALP and GRIm for ESCC. RESULTS HALP was significantly associated with the Zubrod ECOG WHO performance status, tumor location, and the clinical tumor, node, metastasis stage. Modified GRIm (mGRIm) was only significantly associated with metastasis / recurrence before radiotherapy (χ2 = 6.25). Univariate Cox regression analysis showed that higher mGRIm (HR 1.9 95%CI 1.3-2.9) and lower HALP (HR 2.4 95%CI 1.6-3.7) were all associated with worse OS. Multivariate COX analysis found that higher mGRIm score (HR 1.7 95%CI 1.1-2.6), and lower HALP score (HR 2 95%CI 1.3-3.2) were both independent risk factors of overall survival. The nomogram c-index in inside validation was 0.66. CONCLUSION Both HALP and mGRIm are independent prognostic factors for patients with unresectable ESCC.
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Affiliation(s)
- Yujing Shi
- Department of Oncology, Jurong Hospital Affiliated to Jiangsu University, Zhenjiang, Jiangsu, China
| | - Gefenqiang Shen
- Department of Radiotherapy Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Yuting Zeng
- Department of Radiation Oncology, Guizhou Province People Hospital, Guiyang, Guizhou, China
| | - Mengyang Ju
- Department of Radiation Oncology, Osaka University, Suita, Osaka, Japan
| | - Xiaojiao Chen
- Department of Oncology, Jurong Hospital Affiliated to Jiangsu University, Zhenjiang, Jiangsu, China
| | - Chenhong He
- Department of Oncology, Jurong Hospital Affiliated to Jiangsu University, Zhenjiang, Jiangsu, China
| | - Liang Liang
- Department of Oncology, Jurong Hospital Affiliated to Jiangsu University, Zhenjiang, Jiangsu, China
| | - Xiaolin Ge
- Department of Radiotherapy Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Xinchen Sun
- Department of Radiotherapy Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
| | - Xiaoke Di
- Department of Radiotherapy Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
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Gradel KO. Interpretations of the Role of Plasma Albumin in Prognostic Indices: A Literature Review. J Clin Med 2023; 12:6132. [PMID: 37834777 PMCID: PMC10573484 DOI: 10.3390/jcm12196132] [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: 07/07/2023] [Revised: 09/18/2023] [Accepted: 09/21/2023] [Indexed: 10/15/2023] Open
Abstract
This review assesses how publications interpret factors that influence the serum or plasma albumin (PA) level in prognostic indices, focusing on inflammation and nutrition. On PubMed, a search for "albumin AND prognosis" yielded 23,919 results. From these records, prognostic indices were retrieved, and their names were used as search strings on PubMed. Indices found in 10 or more original research articles were included. The same search strings, restricted to "Review" or "Systematic review", retrieved yielded on the indices. The data comprised the 10 latest original research articles and up to 10 of the latest reviews. Thirty indices had 294 original research articles (6 covering two indices) and 131 reviews, most of which were from recent years. A total of 106 articles related the PA level to inflammation, and 136 related the PA level to nutrition. For the reviews, the equivalent numbers were 54 and 65. In conclusion, more publications mention the PA level as a marker of nutrition rather than inflammation. This is in contrast to several general reviews on albumin and nutritional guidelines, which state that the PA level is a marker of inflammation but not nutrition. Hypoalbuminemia should prompt clinicians to focus on the inflammatory aspects in their patients.
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Affiliation(s)
- Kim Oren Gradel
- Center for Clinical Epidemiology, Odense University Hospital, 5000 Odense, Denmark; ; Tel.: +45-21-15-80-85
- Research Unit of Clinical Epidemiology, Department of Clinical Research, University of Southern Denmark, 5000 Odense, Denmark
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15
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Gorgulho J, Roderburg C, Beier F, Bokemeyer C, Brümmendorf TH, Luedde T, Loosen SH. Peripheral blood CD3+HLADR+ cells and associated gut microbiome species predict response and overall survival to immune checkpoint blockade. Front Immunol 2023; 14:1206953. [PMID: 37705980 PMCID: PMC10495594 DOI: 10.3389/fimmu.2023.1206953] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2023] [Accepted: 08/02/2023] [Indexed: 09/15/2023] Open
Abstract
Background The search for biomarkers to identify ideal candidates for immune checkpoint inhibitor (ICI) therapy is fundamental. In this study, we analyze peripheral blood CD3+HLADR+ cells (activated T-cells) as a novel biomarker for ICI therapy and how its association to certain gut microbiome species can indicate individual treatment outcomes. Methods Flow cytometry analysis of peripheral mononuclear blood cells (PBMCs) was performed on n=70 patients undergoing ICI therapy for solid malignancies to quantify HLA-DR on circulating CD3+ cells. 16s-rRNA sequencing of stool samples was performed on n=37 patients to assess relative abundance of gut microbiota. Results Patients with a higher frequency of CD3+HLADR+ cells before treatment initiation showed a significantly reduced tumor response and overall survival (OS), a worst response and experienced less toxicities to ICI therapy. As such, patients with a frequency of CD3+HLADR+ cells above an ideal cut-off value of 18.55% had a median OS of only 132 days compared to 569 days for patients below. Patients with increasing CD3+HLADR+ cell counts during therapy had a significantly improved OS. An immune signature score comprising CD3+HLADR+ cells and the neutrophil-lymphocyte ratio (NLR) was highly significant for predicting OS before and during therapy. When allied to the relative abundance of microbiota from the Burkholderiales order and the species Bacteroides vulgatus, two immune-microbial scores revealed a promising predictive and prognostic power. Conclusion We identify the frequencies and dynamics of CD3+HLADR+ cells as an easily accessible prognostic marker to predict outcome to ICIs, and how these could be associated with immune modulating microbiome species. Two unprecedented immune-microbial scores comprising CD3+HLADR+, NLR and relative abundance of gut bacteria from the Burkhorderiales order or Bacteroides vulgatus species could accurately predict OS to immune checkpoint blockade.
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Affiliation(s)
- Joao Gorgulho
- Department of Oncology, Hematology and Bone Marrow Transplantation with Section of Pneumology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
- Mildred Scheel Cancer Career Center, University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Christoph Roderburg
- Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- Center for Integrated Oncology Aachen-Bonn-Cologne-Düsseldorf (CIOABCD), Aachen, Germany
| | - Fabian Beier
- Center for Integrated Oncology Aachen-Bonn-Cologne-Düsseldorf (CIOABCD), Aachen, Germany
- Department of Medicine IV, University Hospital Rheinisch Westfällisch Technische Hochschule (RWTH) Aachen, Aachen, Germany
| | - Carsten Bokemeyer
- Department of Oncology, Hematology and Bone Marrow Transplantation with Section of Pneumology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
| | - Tim H. Brümmendorf
- Center for Integrated Oncology Aachen-Bonn-Cologne-Düsseldorf (CIOABCD), Aachen, Germany
- Department of Medicine IV, University Hospital Rheinisch Westfällisch Technische Hochschule (RWTH) Aachen, Aachen, Germany
| | - Tom Luedde
- Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- Center for Integrated Oncology Aachen-Bonn-Cologne-Düsseldorf (CIOABCD), Aachen, Germany
| | - Sven H. Loosen
- Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- Center for Integrated Oncology Aachen-Bonn-Cologne-Düsseldorf (CIOABCD), Aachen, Germany
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16
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So WV, Dejardin D, Rossmann E, Charo J. Predictive biomarkers for PD-1/PD-L1 checkpoint inhibitor response in NSCLC: an analysis of clinical trial and real-world data. J Immunother Cancer 2023; 11:jitc-2022-006464. [PMID: 36822668 PMCID: PMC9950975 DOI: 10.1136/jitc-2022-006464] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/07/2022] [Indexed: 02/25/2023] Open
Abstract
BACKGROUND Many biomarkers have been proposed to be predictive of response to anti-programmed cell death protein-1 (PD-1)/anti-programmed death ligand-1 (PD-L1) checkpoint inhibitors (CPI). However, conflicting observations and lack of consensus call for an assessment of their clinical utility in a large data set. Using a combined data set of clinical trials and real-world data, we assessed the predictive and prognostic utility of biomarkers for clinical outcome of CPI in non-small cell lung cancer (NSCLC). METHODS Retrospective cohort study using 24,152 patients selected from 71,850 patients with advanced NSCLC from electronic health records and 9 Roche atezolizumab trials. Patients were stratified into high and low biomarker groups. Correlation with treatment outcome in the different biomarker groups was investigated and compared between patients treated with CPI versus chemotherapy. Durable response was defined as having complete response/partial response without progression during the study period of 270 days. RESULTS Standard blood analytes (eg, albumin and lymphocyte) were just prognostic, having correlation with clinical outcome irrespective of treatment type. High expression of PD-L1 on tumors (≥50% tumor cell staining) were specifically associated with response to CPI (OR 0.20; 95% CI 0.13 to 0.30; p<0.001). The association was stronger in patients with non-squamous than squamous histology, with smoking history than non-smokers, and with prior chemotherapy than first-line CPI. Higher tumor mutational burden (TMB) (≥10.44 mut/Mb) was also specifically associated with durable response to CPI (OR=0.40; 95% CI 0.29 to 0.54; p<0.001). The combination of high TMB and PD-L1 expression was the strongest predictor of durable response to CPI (OR=0.04; 95% CI 0.00 to 0.18; p<0.001). There was no significant association between PD-L1 or TMB levels with response to chemotherapy, suggesting a CPI-specific predictive effect. CONCLUSIONS Standard blood analytes had just prognostic utility, whereas tumor PD-L1 and TMB specifically predicted response to CPI in NSCLC. The combined high TMB and PD-L1 expression was the strongest predictor of durable response. PD-L1 was also a stronger predictor in patients with non-squamous histology, smoking history or prior chemotherapy.
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Affiliation(s)
- WeiQing Venus So
- Data Science, Roche Innovation Center New York, Little Falls, New Jersey, USA
| | - David Dejardin
- Department of Biostatistics, F Hoffmann-La Roche Ltd, Basel, Switzerland
| | - Eva Rossmann
- Roche Innovation Center Basel, F Hoffmann-La Roche Ltd, Basel, Switzerland
| | - Jehad Charo
- Roche Innovation Center Zurich, F Hoffmann-La Roche Ltd, Schlieren, Switzerland
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Loh J, Wu J, Chieng J, Chan A, Yong WP, Sundar R, Lee SC, Wong A, Lim JSJ, Tan DSP, Soo R, Goh BC, Tai BC, Chee CE. Clinical outcome and prognostic factors for Asian patients in Phase I clinical trials. Br J Cancer 2023; 128:1514-1520. [PMID: 36797357 PMCID: PMC10070409 DOI: 10.1038/s41416-023-02193-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2022] [Revised: 01/15/2023] [Accepted: 01/27/2023] [Indexed: 02/18/2023] Open
Abstract
BACKGROUND Patient selection is key in Phase I studies, and prognosis can be difficult to estimate in heavily pre-treated patients. Previous prognostic models like the Royal Marsden Hospital (RMH) score or using the neutrophil-lymphocyte ratio (NLR) have not been validated in current novel therapies nor in the Asian Phase I population. METHODS We conducted a retrospective review of 414 patients with solid tumours participating in Phase I studies at our centre between October 2013 and December 2020. RESULTS The RMH model showed poorer prognosis with increasing scores [RMH score 1, HR 1.28 (95% CI: 0.96-1.70); RMH score 2, HR 2.27 (95% CI: 1.62-3.17); RMH score 3, HR 4.14 (95% CI: 2.62-6.53)]. NLR did not improve the AUC of the model. Poorer ECOG status (ECOG 1 vs. 0: HR = 1.59 (95% CI = 1.24-2.04), P < 0.001) and primary tumour site (GI vs. breast cancer: HR = 3.06, 95% CI = 2.16-4.35, P < 0.001) were prognostic. CONCLUSIONS We developed a NCIS prognostic score with excellent prognostic ability for both short-term and longer-term survival (iAUC: 0.71 [95% CI 0.65-0.76]), and validated the RMH model in the largest Asian study to date.
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Affiliation(s)
- Jerold Loh
- Department of Haematology-Oncology, National University Cancer Institute, Singapore, Singapore
| | - Jiaxuan Wu
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Jenny Chieng
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Aurora Chan
- NUS Saw Swee Hock School of Public Health, Singapore, Singapore
| | - Wei-Peng Yong
- Department of Haematology-Oncology, National University Cancer Institute, Singapore, Singapore
| | - Raghav Sundar
- Department of Haematology-Oncology, National University Cancer Institute, Singapore, Singapore.,Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Soo-Chin Lee
- Department of Haematology-Oncology, National University Cancer Institute, Singapore, Singapore.,Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Andrea Wong
- Department of Haematology-Oncology, National University Cancer Institute, Singapore, Singapore
| | - Joline S J Lim
- Department of Haematology-Oncology, National University Cancer Institute, Singapore, Singapore.,Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - David S P Tan
- Department of Haematology-Oncology, National University Cancer Institute, Singapore, Singapore.,Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Ross Soo
- Department of Haematology-Oncology, National University Cancer Institute, Singapore, Singapore
| | - Boon-Cher Goh
- Department of Haematology-Oncology, National University Cancer Institute, Singapore, Singapore
| | - Bee-Choo Tai
- NUS Saw Swee Hock School of Public Health, Singapore, Singapore
| | - Cheng E Chee
- Department of Haematology-Oncology, National University Cancer Institute, Singapore, Singapore. .,Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
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Lundquist DM, Jimenez R, Durbin S, Horick N, Healy M, Johnson A, Bame V, Capasso V, McIntyre C, Cashavelly B, Juric D, Nipp RD. Identifying Early-Phase Clinical Trial Participants at Risk for Experiencing Worse Clinical Outcomes. JCO Oncol Pract 2023:OP2200742. [PMID: 36791343 DOI: 10.1200/op.22.00742] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/17/2023] Open
Abstract
PURPOSE To identify early-phase clinical trial (EP-CT) participants at risk for experiencing worse clinical outcomes and describe receipt of supportive care services. METHODS A retrospective review of the electronic health records of consecutive patients enrolled in EP-CTs from 2017 to 2019 examined baseline characteristics, clinical outcomes, and receipt of supportive care services. The validated Royal Marsden Hospital (RMH) prognosis score was calculated using data at the time of EP-CT enrollment (scores range from 0 to 3; scores ≥ 2 indicate poor prognosis). Differences in patient characteristics, clinical outcomes, and receipt of supportive care services were compared on the basis of RMH scores. RESULTS Among 350 patients (median age = 63.2 years [range, 23.0-84.3 years], 57.1% female, 98.0% metastatic cancer), 31.7% had an RMH score indicating a poor prognosis. Those with poor prognosis RMH scores had worse overall survival (hazard ratio [HR], 2.00; P < .001), shorter time on trial (HR, 1.53; P < .001), and lower likelihood of completing the dose-limiting toxicity period (odds ratio, 0.42; P = .006) versus those with good prognosis scores. Patients with poor prognosis scores had greater risk of emergency room visits (HR, 1.66; P = .037) and hospitalizations (HR, 1.69; P = .016) while on trial, and earlier hospice enrollment (HR, 2.22; P = .006). Patients with poor prognosis scores were significantly more likely to receive palliative care consultation (46.8% v 27.6%; P < .001), but not other supportive care services. CONCLUSION This study found that RMH prognosis score could identify patients at risk for decreased survival, shorter time on trial, and greater use of health care services. The findings underscore the need to develop supportive care interventions targeting EP-CT participants' distinct needs.
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Affiliation(s)
- Debra M Lundquist
- Cancer Center Protocol Office, Massachusetts General Hospital, Boston, MA
| | - Rachel Jimenez
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA
| | - Sienna Durbin
- Department of Medicine, Division of Hematology and Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA
| | - Nora Horick
- Biostats Center, Massachusetts General Hospital, Boston, MA
| | - Megan Healy
- Cancer Center Protocol Office, Massachusetts General Hospital, Boston, MA
| | - Andrew Johnson
- Cancer Center Protocol Office, Massachusetts General Hospital, Boston, MA
| | - Viola Bame
- Cancer Center Protocol Office, Massachusetts General Hospital, Boston, MA
| | - Virginia Capasso
- Department of Nursing & Patient Care Services, Massachusetts General Hospital, Boston, MA
| | - Casandra McIntyre
- Department of Nursing & Patient Care Services, Massachusetts General Hospital, Boston, MA
| | - Barbara Cashavelly
- Department of Nursing & Patient Care Services, Massachusetts General Hospital, Boston, MA
| | - Dejan Juric
- Department of Medicine, Division of Hematology and Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA
| | - Ryan D Nipp
- University of Oklahoma Stephenson Cancer Center, Oklahoma City, OK
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Systemic Inflammation/Nutritional Status Scores Are Prognostic but Not Predictive in Metastatic Non-Small-Cell Lung Cancer Treated with First-Line Immune Checkpoint Inhibitors. Int J Mol Sci 2023; 24:ijms24043618. [PMID: 36835030 PMCID: PMC9966997 DOI: 10.3390/ijms24043618] [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: 12/22/2022] [Revised: 01/30/2023] [Accepted: 02/08/2023] [Indexed: 02/17/2023] Open
Abstract
Biomarkers of systemic inflammation/nutritional status have been associated with outcomes in advanced-stage non-small-cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs). However, most of them were not tested in cohorts of patients treated with ICIs in combination with chemotherapy (CT) (ICI + CT) or with CT alone, making it impossible to discriminate a predictive from a prognostic effect. We conducted a single-center retrospective study to search for associations between various baseline biomarkers/scores that reflected the systemic inflammation/nutritional status (Lung Immune Prognostic Index, Modified Lung Immune Prognostic Index, Scottish Inflammatory Prognostic Score, Advanced Lung Cancer Inflammation Index, EPSILoN, Prognostic Nutritional Index, Systemic Immune-Inflammation Index, Gustave Roussy Immune Score, Royal Marsden Hospital Prognostic Score, Lung Immuno-oncology Prognostic Score 3, Lung Immuno-oncology Prognostic Score 4, score published by Holtzman et al., and Glasgow Prognostic Score) and outcomes in metastatic NSCLC treated in a first-line setting either with ICI in monotherapy (cohort 1; n = 75), ICI + CT (cohort 2; n = 56), or CT alone (cohort 3; n = 221). In the three cohorts, the biomarkers/scores were moderately associated with overall survival (OS) and progression-free survival (PFS). Their prognostic performance was relatively poor, with a maximum c-index of 0.66. None of them was specific to ICIs and could help to choose the best treatment modality. The systemic inflammation/nutritional status, associated with outcomes independently of the treatment, is therefore prognostic but not predictive in metastatic NSCLC.
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Hatanaka T, Naganuma A, Hiraoka A, Tada T, Hirooka M, Kariyama K, Tani J, Atsukawa M, Takaguchi K, Itobayashi E, Fukunishi S, Tsuji K, Ishikawa T, Tajiri K, Ochi H, Yasuda S, Toyoda H, Ogawa C, Nishimura T, Shimada N, Kawata K, Kosaka H, Kakizaki S, Tanaka T, Ohama H, Nouso K, Morishita A, Tsutsui A, Nagano T, Itokawa N, Okubo T, Arai T, Imai M, Koizumi Y, Nakamura S, Kaibori M, Iijima H, Hiasa Y, Kumada T. The hepatocellular carcinoma modified Gustave Roussy Immune score (HCC-GRIm score) as a novel prognostic score for patients treated with atezolizumab and bevacizumab: A multicenter retrospective analysis. Cancer Med 2023; 12:4259-4269. [PMID: 36156452 PMCID: PMC9972107 DOI: 10.1002/cam4.5294] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2022] [Revised: 09/06/2022] [Accepted: 09/16/2022] [Indexed: 11/10/2022] Open
Abstract
AIM This study investigated whether or not the hepatocellular carcinoma modified Gustave Roussy Immune Score (HCC-GRIm-Score) serves as a prognostic indicator for HCC patients treated with atezolizumab and bevacizumab (Atez/Bev). METHODS A total of 405 HCC patients who received Atez/Bev from September 2020 to January 2022 at 22 different institutions were included in this retrospective study. The HCC-GRIm score was based on the combination of the albumin level (<3.5 g/L = 1 point), lactate dehydrogenase (≥245 U/L = 1 point), neutrophil-to-lymphocyte ratio (≥4.8 = 1 point), aspartate aminotransferase-to-alanine aminotransferase ratio (≥1.44 = 1 point), and total bilirubin level (≥1.3 mg/dl = 1 point). Patients were divided into the low-score group (0, 1, or 2 points) and the high-score group (3, 4, or 5 points). RESULTS There were 89 (22.0%), 141 (34.8%), 106 (26.2%), 49 (12.1%), 16 (4.0%), and 4 (1.0%) patients with scores of 0, 1, 2, 3, 4, 5, respectively. The progression-free survival (PFS) in the low-score group was significantly longer than that in the high-score group (median 7.8 vs. 3.5 months, p < 0.001). The median overall survival (OS) of the low-score group was not reached at the time cutoff, with a 1-year survival rate of 75.5%, whereas the median OS of the high-score group was 8.5 months, showing a significant difference (p < 0.001). A high HCC-GRIm score was a significant unfavorable factor associated with the PFS and OS in multivariate analyses (p = 0.002 and p < 0.001, respectively). CONCLUSIONS The HCC-GRIm score serves as a novel prognostic score for HCC patients treated with Atez/Bev.
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Shangguan J, Huang X, Liu X, Zhang Z, Zhang X, Yu J, Chen D. Gustave Roussy immune score is a prognostic marker in patients with small cell lung cancer undergoing immunotherapy: a real-world retrospective study. Front Oncol 2023; 13:1195499. [PMID: 37205200 PMCID: PMC10187137 DOI: 10.3389/fonc.2023.1195499] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Accepted: 04/18/2023] [Indexed: 05/21/2023] Open
Abstract
Background The utilization of the Gustave Roussy Immune Score (GRIm-Score) in patient selection for immunotherapy was initially reported. The objective of this retrospective study is to assess the potential of the GRIm-Score, a novel prognostic score based on nutritional and inflammatory markers, as a prognostic predictor in patients with small cell lung cancer (SCLC) undergoing immunotherapy. Methods This retrospective study conducted at a single center included 159 patients with SCLC who received immunotherapy. The objective of the study was to investigate potential differences in overall survival (OS) and progression-free survival (PFS) among patients stratified by their GRIm-Score, utilizing the Kaplan-Meier survival analysis and the log-rank test. The final independent prognostic factors were identified through both propensity score matching (PSM) analysis and multivariable Cox proportional hazards regression analysis. Results Our analysis of the 159 patients revealed that there was a significant decrease in both OS and PFS with each increase in the GRIm-Score group, displaying a stepwise pattern. Moreover, even after conducting PSM analysis, the significant associations between the modified three-category risk scale-based GRIm-Score and survival outcomes remained significant. Both the total cohort and PSM cohort were subjected to multivariable analysis, which demonstrated that the three-category risk assessment-based GRIm-Score was a valuable predictor of both OS and PFS. Conclusions In addition, the GRIm-Score may serve as a valuable and non-invasive prognostic predictor for SCLC patients undergoing PD1/PD-L1 immunotherapy.
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Affiliation(s)
- Jian Shangguan
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
- Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Xinyi Huang
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
- Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Xu Liu
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
- Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Zengfu Zhang
- Department of Radiation Oncology, Shandong University Cancer Center, Jinan, Shandong, China
| | - Xiaodong Zhang
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
- Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Jinming Yu
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
- *Correspondence: Dawei Chen, ; Jinming Yu,
| | - Dawei Chen
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
- *Correspondence: Dawei Chen, ; Jinming Yu,
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Zheng M. Serum albumin: a pharmacokinetic marker for optimizing treatment outcome of immune checkpoint blockade. J Immunother Cancer 2022; 10:jitc-2022-005670. [PMID: 36600664 PMCID: PMC9772729 DOI: 10.1136/jitc-2022-005670] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/31/2022] [Indexed: 12/24/2022] Open
Abstract
As we look forward to the bright future of immune checkpoint blockade (ICB) therapy, there is still lacking a pharmacokinetic marker to understand the inter-individual differences in ICB response. ICB therapy is based on IgG antibodies that share the same homeostatic pathway with serum albumin. Therefore, serum albumin level could reflect IgG catabolic rate that directly impacts the clearance of therapeutic IgG antibodies. Through interrogating a large, clinically representative pan-cancer cohort of 1,479 ICB-treated patients, this study found that higher baseline albumin levels were significantly associated with stepwise improvements in overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) (p<0.001), with the variability and reproducibility confirmed in 1,000 bootstrap-resampled cohorts. Furthermore, these findings were also confirmed in most subgroups defined by patient demographics, baseline characteristics, treatments, and cancer types, even in those with low ICB-responsive cancer types and low tumor mutation burden (TMB) (TMB≤10 mut/Mb) that most of which have not been approved by the US Food and Drug Administration (FDA) for ICB therapy. In summary, this study highlights the importance of pretreatment pharmacokinetic modeling for predicting ICB treatment outcomes. Based on serum albumin-an inexpensive, non-invasive, and easily accessible biomarker of IgG pharmacokinetics, we could take a step further towards optimizing ICB therapy.
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Affiliation(s)
- Ming Zheng
- Institute of Military Cognition and Brain Sciences, Academy of Military Medical Sciences, 27 Taiping Road, Beijing 100850, China,Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Beijing 100850, China
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Minichsdorfer C, Gleiss A, Aretin MB, Schmidinger M, Fuereder T. Serum parameters as prognostic biomarkers in a real world cancer patient population treated with anti PD-1/PD-L1 therapy. Ann Med 2022; 54:1339-1349. [PMID: 35535695 PMCID: PMC9103267 DOI: 10.1080/07853890.2022.2070660] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND Immune checkpoint inhibitors (ICI) are regarded as a standard of care in multiple malignancies. We hypothesized that serum parameters are of prognostic value in ICI treated patients suffering from solid tumours. METHODS Data from 114 patients treated with ICIs for solid malignancies from 2015 to 2019 at the Medical University of Vienna were collected retrospectively. Data included baseline characteristics, cancer type, serum parameters such as lactate dehydrogenase (LDH), C-reactive protein (CRP), albumin (Alb) and lymphocyte counts as well as overall survival (OS) and progression free survival. Additionally, the Gustave Roussy Immune Score (GRIm score) and the Glasgow prognostic score (GPS) were calculated. Cox regression models including time-dependent effects and strata for tumour type were used. Prognostic factors were pre-selected using a relaxed LASSO approach. RESULTS The majority of patients were male (64.9%). The most common cancer types were non-small cell lung cancer (30.7%) and renal cell carcinoma (21.9%). Increased LDH and CRP were associated with poor 6-month OS (Hazard ratios (HR)=1.16 and 1.06 per 20% LDH/CRP increase; 95% CI 1.07-1.26 and 95% CI 1.03-1.09, respectively; p < .001). Both GRIm Score and GPS had a significant influence on OS (GRIm: HR = 2.84, 95% CI 1.72-4.69; p < .001 for high vs. low; GPS HR 3.57, 95% CI 1.76-7.25; p < .001 for poor vs. good). The proportion of explained variation (PEV) of our full multivariable model was significantly higher compared to the GRIm and GPS (PEV = 29.5% vs. 14.8% and 14.65%). When grouped into quartiles according to the individual 8-weeks change, both increased LDH and CRP correlated with poor OS (LDH (p=.001) and CRP (p < .001)). CONCLUSION The results of this analysis suggest that serum parameters might have prognostic value for the outcome of cancer patients treated with ICI, regardless of the tumour type.Key messagesIn this retrospective analysis, 114 patients with solid tumours were included. The results of this analysis point out that pre-treatment LDH, CRP and albumin levels are strongly prognostic for a poor 6-month OS.In addition to that, a high GRIm-score and poor GPS were associated with a worse OS (GRIm: HR = 2.84, 95% CI 1.72-4.69; p < .001 for high vs. low; GPS HR = 3.57, 95% CI 1.76-7.25; p < .001 for poor vs. good).Pre-treatment serum parameters might have prognostic value for the outcome of cancer patients treated with ICI, regardless of the tumour type.
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Affiliation(s)
- Christoph Minichsdorfer
- Department of Medicine I & CCC, Division of Oncology, Medical University of Vienna, Wien, Austria
| | - Andreas Gleiss
- Medical University of Vienna, Center for Medical Statistics, Informatics, and Intelligent Systems Institute of Clinical Biometrics, Wien, Austria
| | | | | | - Thorsten Fuereder
- Department of Medicine I & CCC, Division of Oncology, Medical University of Vienna, Wien, Austria
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Banna GL, Friedlaender A, Tagliamento M, Mollica V, Cortellini A, Rebuzzi SE, Prelaj A, Naqash AR, Auclin E, Garetto L, Mezquita L, Addeo A. Biological Rationale for Peripheral Blood Cell-Derived Inflammatory Indices and Related Prognostic Scores in Patients with Advanced Non-Small-Cell Lung Cancer. Curr Oncol Rep 2022; 24:1851-1862. [PMID: 36255605 DOI: 10.1007/s11912-022-01335-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/16/2022] [Indexed: 01/27/2023]
Abstract
PURPOSE OF REVIEW To describe the biological rationale of peripheral blood cells (PBC)-derived inflammatory indexes and assess the related prognostic scores for patients with advanced non-small cell lung cancer (aNSCLC) treated with immune-checkpoint inhibitors (ICI). RECENT FINDINGS Inflammatory indexes based on PBC may indicate a pro-inflammatory condition affecting the immune response to cancer. The lung immune prognostic index (LIPI), consisting of derived neutrophils-to-lymphocyte ratio (NLR) and lactate dehydrogenase, is a validated prognostic tool, especially for pretreated aNSCLC patients, where the combination of NLR and PD-L1 tumour expression might also be predictive of immunotherapy benefit. In untreated high-PD-L1 aNSCLC patients, the Lung-Immune-Prognostic score (LIPS), including NLR, ECOG PS and concomitant steroids, is prognostic, and its modified version might indicate patients with favourable outcomes despite an ECOG PS of 2. NLR times platelets (i.e., SII), included in the NHS-Lung score, might improve the prognostication for combined chemoimmunotherapy. PBC-derived inflammatory indexes and related scores represent accurate, reproducible and non-expensive prognostic tools with clinical and research utility.
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Affiliation(s)
| | - Alex Friedlaender
- Department of Oncology, Clinique Générale Beaulieu, Geneva, Switzerland
- Department of Oncology, University Hospital of Geneva, Geneva, Switzerland
| | - Marco Tagliamento
- Department of Internal Medicine and Medical Specialties (Di.M.I.), University of Genoa, Genoa, Italy
| | - Veronica Mollica
- Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138, Bologna, Italy
| | - Alessio Cortellini
- Division of Cancer, Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, UK
| | - Sara Elena Rebuzzi
- Department of Internal Medicine and Medical Specialties (Di.M.I.), University of Genoa, Genoa, Italy
- Medical Oncology Unit, Ospedale San Paolo, Savona, Italy
| | - Arsela Prelaj
- Medical Oncology Department 1, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
- Department of Electronics, Information, and Bioengineering, Politecnico di Milano, Milan, Italy
| | - Abdul Rafeh Naqash
- Medical Oncology/TSET Phase 1 Program, Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK, USA
| | - Edouard Auclin
- Medical Oncology, Hôpital Européen Georges Pompidou, AP-HP, Université Paris Cité, Paris, France
| | - Lucia Garetto
- Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Turin, Italy
| | - Laura Mezquita
- Medical Oncology Department, Hospital Clinic of Barcelona, Barcelona, Spain
- Laboratory of Translational Genomics and Targeted Therapies in Solid Tumors, IDIBAPS, Barcelona, Spain
- Department of Medicine, University of Barcelona, Barcelona, Spain
| | - Alfredo Addeo
- Department of Oncology, University Hospital of Geneva, Geneva, Switzerland
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Rebuzzi SE, Prelaj A, Friedlaender A, Cortellini A, Addeo A, Genova C, Naqash AR, Auclin E, Mezquita L, Banna GL. Prognostic scores including peripheral blood-derived inflammatory indices in patients with advanced non-small-cell lung cancer treated with immune checkpoint inhibitors. Crit Rev Oncol Hematol 2022; 179:103806. [PMID: 36087850 DOI: 10.1016/j.critrevonc.2022.103806] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Revised: 08/28/2022] [Accepted: 09/05/2022] [Indexed: 10/31/2022] Open
Abstract
Peripheral blood inflammatory indices, like the neutrophil-to-lymphocyte ratio (NLR), may reflect the host's pro-inflammatory status and systemic immune response to cancer-related inflammation. We reviewed 22 combined prognostic scores based on peripheral blood-derived inflammatory indices for aNSCLC patients treated with single-agent or combination immune-checkpoint inhibitors (ICI) as first-line or subsequent therapy lines and attempted evidence strength assessment and scoring. The Lung Immune Prognostic Index (LIPI), consisting of derived NLR and LDH, was the most studied score with validated prognostic value in over five thousand aNSCLC ICI-naïve or pretreated patients. The combination of NLR and tumour programmed-cell-death-ligand1 (PD-L1) expression showed a predictive value. The Lung-Immune-Prognostic score (LIPS) might help identify patients with poor performance status but a favourable outcome following first-line ICI. These non-expensive scores can help clinicians discuss the prognosis with aNSCLC patients approaching ICI, identify those less likely to benefit from single-agent ICI and orient future clinical research.
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Affiliation(s)
- Sara Elena Rebuzzi
- Medical Oncology Unit, Ospedale San Paolo, Savona, Italy; Department of Internal Medicine and Medical Specialties (Di.M.I.), University of Genoa, Genoa, Italy
| | - Arsela Prelaj
- Medical Oncology Department 1, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy; Department of Electronics, Information, and Bioengineering, Politecnico di Milano, Milan, Italy
| | - Alex Friedlaender
- Department of Oncology, Clinique Générale Beaulieu, Geneva, Switzerland; Department of Oncology, University Hospital of Geneva, Geneva, Switzerland
| | - Alessio Cortellini
- Division of Cancer, Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, UK
| | - Alfredo Addeo
- Department of Oncology, University Hospital of Geneva, Geneva, Switzerland
| | - Carlo Genova
- Department of Internal Medicine and Medical Specialties (Di.M.I.), University of Genoa, Genoa, Italy; UOC Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Abdul Rafeh Naqash
- Medical Oncology/TSET Phase 1 Program, Stephenson Cancer Center, University of Oklahoma, Oklahoma City, USA
| | - Edouard Auclin
- Medical Oncology, Hôpital Européen Georges Pompidou, AP-HP, Université Paris Cité, Paris, France
| | - Laura Mezquita
- Medical Oncology Department, Hospital Clinic of Barcelona, Spain; Laboratory of Translational Genomics and Targeted Therapies in Solid Tumors, IDIBAPS, Spain; Department of Medicine, University of Barcelona, Spain
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Guven DC, Sahin TK, Erul E, Cakir IY, Ucgul E, Yildirim HC, Aktepe OH, Erman M, Kilickap S, Aksoy S, Yalcin S. The Association between Early Changes in Neutrophil-Lymphocyte Ratio and Survival in Patients Treated with Immunotherapy. J Clin Med 2022; 11:4523. [PMID: 35956139 PMCID: PMC9369683 DOI: 10.3390/jcm11154523] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Revised: 07/15/2022] [Accepted: 07/24/2022] [Indexed: 02/05/2023] Open
Abstract
Dynamic changes in the blood-based biomarkers could be used as a prognostic biomarker in patients treated with immune checkpoint inhibitors (ICIs), although the data are limited. We evaluated the association between the neutrophil−lymphocyte ratio (NLR) and early NLR changes with survival in ICI-treated patients. We retrospectively evaluated the data of 231 patients with advanced-stage cancer. We recorded baseline clinical characteristics, baseline NLR and fourth-week NLR changes, and survival data. A compound prognostic score, the NLR2-CEL score, was developed with the following parameters: baseline NLR (<5 vs. ≥5), ECOG status (0 vs. ≥1), Charlson Comorbidity Index (CCI, <9 vs. ≥9), LDH (N vs. ≥ULN), and fourth-week NLR change (10% or over NLR increase). In the multivariable analyses, higher NLR (HR: 1.743, p = 0.002), 10% or over NLR increase in the fourth week of treatment (HR: 1.807, p = 0.001), higher ECOG performance score (HR: 1.552, p = 0.006), higher LDH levels (HR: 1.454, p = 0.017), and higher CCI (HR: 1.400, p = 0.041) were associated with decreased OS. Compared to patients with the lowest scores, patients in the highest score group had significantly lower OS (HR: 7.967, 95% CI: 3.531−17.979, p < 0.001) and PFS. The composite score had moderate success for survival prediction, with an AUC of 0.702 (95% CI: 0.626−0.779, p < 0.001). We observed significantly lower survival in patients with higher baseline NLR values and increased NLR values under treatment.
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Affiliation(s)
- Deniz Can Guven
- Department of Medical Oncology, Cancer Institute, Hacettepe University, 06100 Ankara, Turkey; (H.C.Y.); (O.H.A.); (M.E.); (S.K.); (S.A.); (S.Y.)
| | - Taha Koray Sahin
- Department of Internal Medicine, Faculty of Medicine, Hacettepe University, 06100 Ankara, Turkey; (T.K.S.); (E.E.); (I.Y.C.); (E.U.)
| | - Enes Erul
- Department of Internal Medicine, Faculty of Medicine, Hacettepe University, 06100 Ankara, Turkey; (T.K.S.); (E.E.); (I.Y.C.); (E.U.)
| | - Ibrahim Yahya Cakir
- Department of Internal Medicine, Faculty of Medicine, Hacettepe University, 06100 Ankara, Turkey; (T.K.S.); (E.E.); (I.Y.C.); (E.U.)
| | - Enes Ucgul
- Department of Internal Medicine, Faculty of Medicine, Hacettepe University, 06100 Ankara, Turkey; (T.K.S.); (E.E.); (I.Y.C.); (E.U.)
| | - Hasan Cagri Yildirim
- Department of Medical Oncology, Cancer Institute, Hacettepe University, 06100 Ankara, Turkey; (H.C.Y.); (O.H.A.); (M.E.); (S.K.); (S.A.); (S.Y.)
| | - Oktay Halit Aktepe
- Department of Medical Oncology, Cancer Institute, Hacettepe University, 06100 Ankara, Turkey; (H.C.Y.); (O.H.A.); (M.E.); (S.K.); (S.A.); (S.Y.)
| | - Mustafa Erman
- Department of Medical Oncology, Cancer Institute, Hacettepe University, 06100 Ankara, Turkey; (H.C.Y.); (O.H.A.); (M.E.); (S.K.); (S.A.); (S.Y.)
| | - Saadettin Kilickap
- Department of Medical Oncology, Cancer Institute, Hacettepe University, 06100 Ankara, Turkey; (H.C.Y.); (O.H.A.); (M.E.); (S.K.); (S.A.); (S.Y.)
- Department of Medical Oncology, Faculty of Medicine, Istinye University, 34396 Istanbul, Turkey
| | - Sercan Aksoy
- Department of Medical Oncology, Cancer Institute, Hacettepe University, 06100 Ankara, Turkey; (H.C.Y.); (O.H.A.); (M.E.); (S.K.); (S.A.); (S.Y.)
| | - Suayib Yalcin
- Department of Medical Oncology, Cancer Institute, Hacettepe University, 06100 Ankara, Turkey; (H.C.Y.); (O.H.A.); (M.E.); (S.K.); (S.A.); (S.Y.)
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Nakazawa N, Sohda M, Ubukata Y, Kuriyama K, Kimura A, Kogure N, Hosaka H, Naganuma A, Sekiguchi M, Saito K, Ogata K, Sano A, Sakai M, Ogawa H, Shirabe K, Saeki H. Changes in the Gustave Roussy Immune Score as a Powerful Prognostic Marker of the Therapeutic Sensitivity of Nivolumab in Advanced Gastric Cancer: A Multicenter, Retrospective Study. Ann Surg Oncol 2022; 29:7400-7406. [PMID: 35857197 DOI: 10.1245/s10434-022-12226-4] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Accepted: 06/25/2022] [Indexed: 12/14/2022]
Abstract
BACKGROUND Identification of positive biomarkers for the effects of nivolumab on patients with advanced gastric cancer (AGC) is significant. The Gustave Roussy Immune Score (GRIm-s) is associated with therapeutic resistance of immune checkpoint inhibitors (ICIs) in other cancers. This multicenter, retrospective study was designed to analyze the association of GRIm-s with therapeutic sensitivity of nivolumab in patients with AGC. METHODS We reviewed 58 patients with AGC treated with nivolumab from October 2017 to November 2018 at five participating institutions. We performed blood tests before the start of nivolumab and after administration of two courses. We evaluated the correlation between the best overall response and GRIm-s. Additionally, we focused on the changes in GRIm-s before the start of nivolumab and after administration of two courses. RESULTS Of the 58 patients, 21 (36.2%) were classified into the disease control (DC) group and 37 (63.8%) into the progressive disease (PD) group. GRIm-s before nivolumab treatment did not correlate with the best therapeutic response (p = 0.086). However, GRIm-s after two courses of nivolumab showed that significantly more PD cases were in the high-risk group (p < 0.0001). After two courses of nivolumab, overall survival was significantly worse in the high-risk group (p < 0.0001). For progression-free survival, the high-risk group had a significantly worse prognosis both before (p = 0.04) and after two courses of nivolumab treatment (p < 0.0001). CONCLUSIONS GRIm-s after two courses of nivolumab and its changes compared to pretreatment values proved beneficial in predicting nivolumab sensitivity.
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Affiliation(s)
- Nobuhiro Nakazawa
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan
| | - Makoto Sohda
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan.
| | - Yasunari Ubukata
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan
| | - Kengo Kuriyama
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan
| | - Akiharu Kimura
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan
| | - Norimichi Kogure
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan
| | - Hisashi Hosaka
- Department of Gastroenterology, Gunma Prefectural Cancer Center, Ota, Gunma, Japan
| | - Atsushi Naganuma
- Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, Takasaki, Gunma, Japan
| | - Masanori Sekiguchi
- Department of Gastroenterology, Isesaki Municipal Hospital, Isesaki, Gunma, Japan
| | - Kana Saito
- Department of Surgery, Japan Community Healthcare Organization Gunma Central Hospital, Maebashi, Gunma, Japan
| | - Kyoichi Ogata
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan
| | - Akihiko Sano
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan
| | - Makoto Sakai
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan
| | - Hiroomi Ogawa
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan
| | - Ken Shirabe
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan
| | - Hiroshi Saeki
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan
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Li Y, Pan Y, Lin X, Hou J, Hu Z, Xu L, Zhou Z, Zhang Y, Chen M, Hu D. Development and Validation of a Prognostic Score for Hepatocellular Carcinoma Patients in Immune Checkpoint Inhibitors Therapies: The Hepatocellular Carcinoma Modified Gustave Roussy Immune Score. Front Pharmacol 2022; 12:819985. [PMID: 35237150 PMCID: PMC8883391 DOI: 10.3389/fphar.2021.819985] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Accepted: 12/24/2021] [Indexed: 12/12/2022] Open
Abstract
Background: There is not yet an effective marker in predicting the efficacy of immune checkpoint inhibitors (ICIs) in treating hepatocellular carcinoma (HCC) patients. The Gustave Roussy Immune Score (GRIm-Score) based on three objective variables, namely, neutrophil-to-lymphocyte ratio (NLR), serum albumin level (ALB), and lactate dehydrogenase (LDH), was developed as feasible prognostic indication in lung cancer patients receiving ICIs therapies. Our study aimed to adapt the GRIm-Score (HCC-GRIm-Score) in HCC patients who received ICIs therapies and thus improving the predictive ability. Methods: From January 2018 to September 2020, 261 patients who received ICIs therapy were retrospectively included and divided into training and validation groups. After determining the factors for HCC-GRIm-Score by multivariable analysis from training group, the optimized HCC-GRIm-Score was validated and compared to the original GRIm-Score and the Barcelona clinic liver cancer (BCLC) staging system. Results: One hundred sixty-one and 80 patients were assigned into the training and validation groups, respectively. Two more factors, aspartate transaminase-to-alanine transaminase ratio [hazard ratio (HR), 1.51; 95% confidence interval (CI), 0.94–2.42] and total bilirubin (HR, 1.76; 95% CI, 1.07–2.88), were identified as independent prognostic factors for overall survival (OS) and integrated in the HCC-GRIm-Score system according to the multivariable analysis. A risk score based on the HCC-GRIm-Score indicated that patients presenting high score (>2) suffered from significantly shorter median OS of 10.3 months compared to those with a low score (not reached; HR, 2.99; 95% CI, 1.89–4.75; p < 0.001). In the validation group of 80 patients, the patients presenting a high score showed an inferior OS (HR 5.62, 95% CI, 1.25–25.24; p = 0.024). HCC-GRIm-Score had the highest area under curve of 0.719 (95% CI, 0.661–0.773) compared to original GRIm-Score and BCLC staging system. Conclusion: The present study confirmed that the modified HCC-GRIm-Score system provided superior predictive ability in identifying the HCC patients potentially benefit from ICIs therapies, compared to the original GRIm-Score and the BCLC staging system.
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Affiliation(s)
- Yongjiang Li
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.,Department of Nuclear Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Yangxun Pan
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.,Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Ximeng Lin
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.,Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Jingyu Hou
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.,Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Zili Hu
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.,Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Li Xu
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.,Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Zhongguo Zhou
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.,Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Yaojun Zhang
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.,Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Minshan Chen
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.,Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Dandan Hu
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.,Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, China
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Li M, Kaili D, Shi L. Biomarkers for response to immune checkpoint inhibitors in gastrointestinal cancers. World J Gastrointest Oncol 2022; 14:19-37. [PMID: 35116101 PMCID: PMC8790411 DOI: 10.4251/wjgo.v14.i1.19] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 09/08/2021] [Accepted: 12/21/2021] [Indexed: 02/06/2023] Open
Abstract
Gastrointestinal (GI) cancers account for a large proportion of cancer deaths worldwide and pose a major public health challenge. Immunotherapy is considered to be one of the prominent and successful approaches in cancer treatment in recent years. Among them, immune checkpoint inhibitor (ICI) therapy, has received widespread attention, and many clinical findings support the feasibility of ICIs, with sustained responses and significantly prolonged lifespan observed in a wide range of tumors. However, patients treated with ICIs have not fully benefited, and therefore, the identification and development of biomarkers for predicting ICI treatment response have received further attention and exploration. From tumor genome to molecular interactions in the tumor microenvironment, and further expanding to circulating biomarkers and patient characteristics, the exploration of biomarkers is evolving with high-throughput sequencing as well as bioinformatics. More large-scale prospective and specific studies are needed to explore biomarkers in GI cancers. In this review, we summarize the known biomarkers used in ICI therapy for GI tumors. In addition, some ICI biomarkers applied to other tumors are included to provide insights and further validation for GI tumors. Moreover, we present single-cell analysis and machine learning approaches that have emerged in recent years. Although there are no clear applications yet, it can be expected that these techniques will play an important role in the application of biomarker prediction.
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Affiliation(s)
- Meng Li
- School of Life Sciences, Chongqing University, Chongqing 400044, China
| | - Denis Kaili
- Department of Surgery, Wexner Medical Center, The Ohio State University, Columbus, OH 43210, United States
| | - Lei Shi
- School of Life Sciences, Chongqing University, Chongqing 400044, China
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30
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Tian S, Cao Y, Duan Y, Liu Q, Peng P. Gustave Roussy Immune Score as a Novel Prognostic Scoring System for Colorectal Cancer Patients: A Propensity Score Matching Analysis. Front Oncol 2021; 11:737283. [PMID: 34917499 PMCID: PMC8669102 DOI: 10.3389/fonc.2021.737283] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Accepted: 11/08/2021] [Indexed: 12/26/2022] Open
Abstract
Aim The Gustave Roussy Immune Score (GRIm-Score) was originally designed to select cancer patients for immunotherapy, and later was reported to be a novel prognostic scoring system in lung cancer and esophageal cancer. This study was aimed to determine the prognostic role and predictive performance of GRIm-Score in colorectal cancer (CRC) CRC patients. Methods We conducted a single-institution study of 1,579 adult CRC patients receiving surgical removal, and those patients were divided into low GRIm-Score group (scores 0, 1) and high GRIm-Score group (scores 2, 3). Propensity score matching (PSM) was executed to balance the potential confounding factors between the two groups. Survival and time-dependent receiver operating characteristic (Td-ROC) analyses were applied to depict the prognostic role and predictive significance of GRIm-Score in CRC patients. Results There were 200 cases CRC patients in high GRIm-Score group and 1,379 cases in low GRIm-Score group. CRC patients with high GRIm-Score correspond with higher level of CEA, CA125, and inflammatory indexes, such as NLR, PLR, SII, PNI, and ALRI. Correlation analysis exhibited that GRIm-Score correlated well with the established inflammatory indexes. Survival analysis revealed that CRC patients in high GRIm-Score group showed worse overall survival (OS, P <0.0001) and disease-free survival (DFS, P <0.0001) compared with those in low GRIm-Score group. Results from multivariate Cox regression implicated that high GRIm-Score was not only a potent prognostic index for unfavorable OS (HR = 1.622, 95%CI: 1.118–2.355, P = 0.0109), but also a potent risk factor for worse DFS (HR = 1.743, 95%CI: 1.188–2.558, P = 0.0045). Td-ROC analysis demonstrated that GRIm-Score exhibited the superior discriminatory power in the prediction of OS and DFS when compared to SII, PNI, and ALRI. Such strong associations between high levels of preoperative GRIm-Score and unfavorable survival outcomes remained robust after PSM analysis. Conclusion GRIm-Score, a novel inflammatory and nutritional risk scoring system, is a potent prognostic index in CRC patients receiving surgical removal. GRIm-Score can be used as an effective and simplified risk stratification tool for postoperative survival prediction of CRC patients.
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Affiliation(s)
- Shan Tian
- Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yinghao Cao
- Department of Colorectal Surgery and Gastroenterology, Wuhan Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China
| | - Yanran Duan
- Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Qi Liu
- Department of Gastroenterology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China
| | - Pailan Peng
- Department of Gastroenterology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China
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31
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Egal ESA, Jacenik D, Soares HP, Beswick EJ. Translational challenges in pancreatic neuroendocrine tumor immunotherapy. Biochim Biophys Acta Rev Cancer 2021; 1876:188640. [PMID: 34695532 PMCID: PMC10695297 DOI: 10.1016/j.bbcan.2021.188640] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2021] [Revised: 09/19/2021] [Accepted: 10/18/2021] [Indexed: 12/28/2022]
Abstract
Pancreatic neuroendocrine tumors are rare types of pancreatic cancer formed from islet cells of pancreas. Clinical presentation of pancreatic neuroendocrine tumors depends on both tumor progression and hormone secretion status, which generate several complications in both diagnosis and treatment. Despite numerous strategies, treatment of patients with pancreatic neuroendocrine tumors still needs improvement. It is suggested that immune response modulation may be essential in the regulation of pancreatic neuroendocrine tumor progression and patient's symptomology. Accumulating evidence indicates that immunotherapy seems to be a promising treatment option for patients with pancreatic neuroendocrine tumors. Nevertheless, several challenges in pre-clinical and clinical studies are present. This review provides knowledge about microenvironment of pancreatic neuroendocrine tumors including significance of cytokine and chemokine as well as specific immune cell types. Additionally, in vitro and in vivo models of pancreatic neuroendocrine tumors and translational challenges are highlighted.
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Affiliation(s)
- Erika Said Abu Egal
- Division of Gastroenterology, Department of Internal Medicine, University of Utah, UT, Salt Lake City, United States
| | - Damian Jacenik
- Division of Gastroenterology, Department of Internal Medicine, University of Utah, UT, Salt Lake City, United States; Division of Oncology, Department of Internal Medicine, Huntsman Cancer Institute at the University of Utah, UT, Salt Lake City, United States; Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland
| | - Heloisa Prado Soares
- Division of Oncology, Department of Internal Medicine, Huntsman Cancer Institute at the University of Utah, UT, Salt Lake City, United States.
| | - Ellen J Beswick
- Division of Gastroenterology, Department of Internal Medicine, University of Utah, UT, Salt Lake City, United States
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32
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Möller M, Turzer S, Schütte W, Seliger B, Riemann D. Blood Immune Cell Biomarkers in Patient With Lung Cancer Undergoing Treatment With Checkpoint Blockade. J Immunother 2021; 43:57-66. [PMID: 31592989 PMCID: PMC7012348 DOI: 10.1097/cji.0000000000000297] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Supplemental Digital Content is available in the text. Characterization of host immune cell parameters before and during immunotherapy is expected to identify predictive biomarkers for clinical outcome. We prospectively monitored blood immune cells from 35 patients with advanced non–small cell lung cancer undergoing checkpoint inhibitor monotherapy. The aim was to identify parameters correlating with better/worse outcome. Peripheral blood was serially collected before each infusion at the onset and at cycle 3 and 5 of immunotherapy. A complete leukocyte blood count, the lymphocytic subpopulations and the percentages of both HLA-DRlow monocytes and dendritic cells (DC) were monitored. Disease control was defined as partial/complete response and stable disease on computed tomography scan according to RECIST 1.1. The predictive value of the immune cell parameters investigated was evaluated by patients’ survival analysis. Forty percent of patients showed a clinical response, and the global median overall survival was 7.0 months (95% confidence interval: 3.5–10.5). Patients with an initial neutrophil-to-lymphocyte ratio (NLR) ≥5.2, and/or an amount of HLA-DRlow monocytes ≥11% and/or a total DC level ≤0.4% of leukocytes did rarely respond to PD-1 inhibitor therapy. Otherwise, the immunotherapy-induced decrease of the neutrophil-to-lymphocyte ratio and/or HLA-DRlow monocytes and the increase of total DC frequencies were correlated with improved therapy response and prolonged overall survival. Blood values in the third cycle of immunotherapy did already reflect the effects observed. On the basis of the 3 immune cell parameters identified we created 3 different variants of scores that enable to stratify patients into groups of risk/therapy response. Our results warrant further investigation in larger prospective clinical trials for validation.
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Affiliation(s)
- Miriam Möller
- Clinic of Internal Medicine, Hospital Martha-Maria Halle-Dölau
| | - Steffi Turzer
- Institute of Medical Immunology, Martin Luther University Halle-Wittenberg, Halle, Germany
| | | | - Barbara Seliger
- Institute of Medical Immunology, Martin Luther University Halle-Wittenberg, Halle, Germany
| | - Dagmar Riemann
- Institute of Medical Immunology, Martin Luther University Halle-Wittenberg, Halle, Germany
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Nenclares P, Gunn L, Soliman H, Bover M, Trinh A, Leslie I, Wong KH, Melcher A, Newbold K, Nutting CM, Ap Dafydd D, Bhide SA, Harrington K. On-treatment immune prognostic score for patients with relapsed and/or metastatic head and neck squamous cell carcinoma treated with immunotherapy. J Immunother Cancer 2021; 9:e002718. [PMID: 34103355 PMCID: PMC8190047 DOI: 10.1136/jitc-2021-002718] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/06/2021] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Previous studies have suggested that inflammatory markers (neutrophil-to-lymphocyte ratio (NLR), lactate dehydrogenase (LDH) and fibrinogen) are prognostic biomarkers in patients with a variety of solid cancers, including those treated with immune checkpoint inhibitors (ICIs). We aimed to develop a model that predicts response and survival in patients with relapsed and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) treated with immunotherapy. METHODS Analysis of 100 consecutive patients with unresectable R/M HNSCC who were treated with ICI. Baseline and on-treatment (day 28) NLR, fibrinogen and LDH were calculated and correlated with response, progression-free survival (PFS) and overall survival (OS) using univariate and multivariate analyses. The optimal cut-off values were derived using maximally selected log-rank statistics. RESULTS Low baseline NLR and fibrinogen levels were associated with response. There was a statistically significant correlation between on-treatment NLR and fibrinogen and best overall response. On-treatment high NLR and raised fibrinogen were significantly associated with poorer outcome. In multivariate analysis, on-treatment NLR (≥4) and on-treatment fibrinogen (≥4 ng/mL) showed a significant negative correlation with OS and PFS. Using these cut-off points, we generated an on-treatment score for OS and PFS (0-2 points). The derived scoring system shows appropriate discrimination and suitability for OS (HR 2.4, 95% CI 1.7 to 3.4, p<0.0001, Harrell's C 0.67) and PFS (HR 1.8, 95% CI 1.4 to 2.3, p<0.0001, Harrell's C 0.68). In the absence of an external validation cohort, results of fivefold cross-validation of the score and evaluation of median OS and PFS on the Kaplan-Meier survival distribution between trained and test data exhibited appropriate accuracy and concordance of the model. CONCLUSIONS NLR and fibrinogen levels are simple, inexpensive and readily available biomarkers that could be incorporated into an on-treatment scoring system and used to help predict survival and response to ICI in patients with R/M HNSCC.
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Affiliation(s)
- Pablo Nenclares
- Head and Neck Unit, Royal Marsden Hospital NHS Trust, London, UK
- Division of Radiotherapy and Imaging, The Institute of Cancer Research, London, UK
| | - Lucinda Gunn
- Head and Neck Unit, Royal Marsden Hospital NHS Trust, London, UK
| | - Heba Soliman
- Head and Neck Unit, Royal Marsden Hospital NHS Trust, London, UK
| | - Mateo Bover
- Head and Neck Unit, Hospital Universitario 12 de Octubre, Madrid, Spain
| | - Amy Trinh
- Head and Neck Unit, Royal Marsden Hospital NHS Trust, London, UK
| | - Isla Leslie
- Head and Neck Unit, Royal Marsden Hospital NHS Trust, London, UK
| | - Kee Howe Wong
- Head and Neck Unit, Royal Marsden Hospital NHS Trust, London, UK
| | - Alan Melcher
- Head and Neck Unit, Royal Marsden Hospital NHS Trust, London, UK
- Division of Radiotherapy and Imaging, The Institute of Cancer Research, London, UK
| | - Kate Newbold
- Head and Neck Unit, Royal Marsden Hospital NHS Trust, London, UK
| | - Chris M Nutting
- Head and Neck Unit, Royal Marsden Hospital NHS Trust, London, UK
| | - Derfel Ap Dafydd
- Head and Neck Unit, Royal Marsden Hospital NHS Trust, London, UK
| | - Shreerang A Bhide
- Head and Neck Unit, Royal Marsden Hospital NHS Trust, London, UK
- Division of Radiotherapy and Imaging, The Institute of Cancer Research, London, UK
| | - Kevin Harrington
- Head and Neck Unit, Royal Marsden Hospital NHS Trust, London, UK
- Division of Radiotherapy and Imaging, The Institute of Cancer Research, London, UK
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Prediction of prognosis of patients with lung cancer in combination with the immune score. Biosci Rep 2021; 41:228143. [PMID: 33764442 PMCID: PMC8128102 DOI: 10.1042/bsr20203431] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2020] [Revised: 03/16/2021] [Accepted: 03/23/2021] [Indexed: 01/19/2023] Open
Abstract
PURPOSE The host's immune response to malignant tumor is fundamental to tumorigenesis and tumor development. The immune score is currently used to assess prognosis and to guide immunotherapy; however, its association with lung cancer prognosis is not clear. METHODS Clinical features and immune score data of lung cancer patients from The Cancer Genome Atlas were obtained to build a clinical prognosis nomogram. The model's accuracy was verified by calibration curves. RESULTS In total, 1005 patients with lung cancer were included. Patients were divided into three groups according to low, medium, and high immune scores. Compared with patients in the low immune score group, the disease-free survival (DFS) of patients in medium and high immune score groups was significantly longer; the hazard ratio (HR) and 95% confidence interval (95% CI) were 0.77 [0.60-0.99] and 0.74 [0.60-0.91], respectively. The overall survival (OS) of patients in the medium and high immune score groups was significantly longer than in the low immune score group; the HR and 95% CI were 0.74 [0.57-0.96] and 0.69 [0.55-0.88], respectively. A clinical prediction model was established to predict the survival prognosis. As verified by calibration curves, the model showed good predictive ability, especially for predicting 3-/5-year DFS and OS. CONCLUSION Patients with lung cancer with medium and high immune scores had longer DFS and OS than those in low immune score group. Patient prognosis can be effectively predicted by the clinical prediction model combining clinical features and immune score and was consistent with actual clinical outcomes.
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Lenci E, Cantini L, Pecci F, Cognigni V, Agostinelli V, Mentrasti G, Lupi A, Ranallo N, Paoloni F, Rinaldi S, Nicolardi L, Caglio A, Aerts S, Cortellini A, Ficorella C, Chiari R, Di Maio M, Dingemans AMC, Aerts JGJV, Berardi R. The Gustave Roussy Immune (GRIm)-Score Variation Is an Early-on-Treatment Biomarker of Outcome in Advanced Non-Small Cell Lung Cancer (NSCLC) Patients Treated with First-Line Pembrolizumab. J Clin Med 2021; 10:1005. [PMID: 33801320 PMCID: PMC7958321 DOI: 10.3390/jcm10051005] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2021] [Revised: 02/11/2021] [Accepted: 02/13/2021] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND The Gustave Roussy Immune (GRIm)-Score takes into account neutrophil-to-lymphocyte ratio (NLR), serum albumin concentration and lactate dehydrogenase (LDH) and its prognostic value has been investigated in patients treated with immune check-point inhibitors (ICIs). To further assess the prognostic and predictive value of baseline GRIm-Score (GRImT0) in advanced non-small cell lung cancer (aNSCLC) patients, we separately investigated two cohorts of patients treated with first-line pembrolizumab or chemotherapy. We also investigated whether GRIm-Score at 45 days since treatment initiation (GRImT1) and GRIm-Score difference between the two timepoints may better predict clinical outcomes (GRImΔ = GRImT0 - GRImT1). METHODS We retrospectively evaluated 222 aNSCLC patients: 135 treated with pembrolizumab and 87 treated with chemotherapy as the first-line regimen. NLR, serum albumin and LDH concentrations were assessed at T0 and at T1. According to the GRIm-Score, patients were assigned 1 point if they had NLR > 6, LDH > upper limit normal or albumin < 3.5 g/dL. Patients with a GRIm-Score < 2 were considered as having a low Score. RESULTS In both cohorts, no difference in terms of overall survival (OS) between patients with low and high GRImT0 was found. Otherwise, median OS and progression free survival (PFS) of the low GRImT1 group were significantly longer than those of the high GRImT1 group in pembrolizumab-treated patients, but not in the CHT cohort (pembrolizumab cohort: low vs. high; median OS not reached vs. 9.2 months, p = 0.004; median PFS 10.8 vs. 2.3 months, p = 0.002). Patients receiving pembrolizumab with stable/positive GRImΔ had better OS (median OS not reached vs. 12.0 months, p < 0.001), PFS (median PFS 20.6 vs. 2.6 months, p < 0.001) and objective response rate (58.2% vs. 7.6%, p = 0.003) compared to patients with negative GRImΔ. CONCLUSION Our data shown that GRImT1 and GRImΔ are more reliable peripheral blood biomarkers of outcome compared to GRImT0 in aNSCLC patients treated with pembrolizumab and might represent useful biomarkers to drive clinical decisions in this setting.
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Affiliation(s)
- Edoardo Lenci
- Department of Medical Oncology, Università Politecnica delle Marche, AOU Ospedali Riuniti Ancona, 60126 Ancona, Italy; (E.L.); (L.C.); (F.P.); (V.C.); (V.A.); (G.M.); (A.L.); (N.R.); (F.P.); (S.R.)
| | - Luca Cantini
- Department of Medical Oncology, Università Politecnica delle Marche, AOU Ospedali Riuniti Ancona, 60126 Ancona, Italy; (E.L.); (L.C.); (F.P.); (V.C.); (V.A.); (G.M.); (A.L.); (N.R.); (F.P.); (S.R.)
- Department of Pulmonary Medicine, Erasmus MC Rotterdam, 3015 GD Rotterdam, The Netherlands; (S.A.); (A.-M.C.D.); (J.G.J.V.A.)
- Erasmus MC Cancer Institute, Erasmus MC Rotterdam, 3015 GD Rotterdam, The Netherlands
| | - Federica Pecci
- Department of Medical Oncology, Università Politecnica delle Marche, AOU Ospedali Riuniti Ancona, 60126 Ancona, Italy; (E.L.); (L.C.); (F.P.); (V.C.); (V.A.); (G.M.); (A.L.); (N.R.); (F.P.); (S.R.)
| | - Valeria Cognigni
- Department of Medical Oncology, Università Politecnica delle Marche, AOU Ospedali Riuniti Ancona, 60126 Ancona, Italy; (E.L.); (L.C.); (F.P.); (V.C.); (V.A.); (G.M.); (A.L.); (N.R.); (F.P.); (S.R.)
| | - Veronica Agostinelli
- Department of Medical Oncology, Università Politecnica delle Marche, AOU Ospedali Riuniti Ancona, 60126 Ancona, Italy; (E.L.); (L.C.); (F.P.); (V.C.); (V.A.); (G.M.); (A.L.); (N.R.); (F.P.); (S.R.)
| | - Giulia Mentrasti
- Department of Medical Oncology, Università Politecnica delle Marche, AOU Ospedali Riuniti Ancona, 60126 Ancona, Italy; (E.L.); (L.C.); (F.P.); (V.C.); (V.A.); (G.M.); (A.L.); (N.R.); (F.P.); (S.R.)
| | - Alessio Lupi
- Department of Medical Oncology, Università Politecnica delle Marche, AOU Ospedali Riuniti Ancona, 60126 Ancona, Italy; (E.L.); (L.C.); (F.P.); (V.C.); (V.A.); (G.M.); (A.L.); (N.R.); (F.P.); (S.R.)
| | - Nicoletta Ranallo
- Department of Medical Oncology, Università Politecnica delle Marche, AOU Ospedali Riuniti Ancona, 60126 Ancona, Italy; (E.L.); (L.C.); (F.P.); (V.C.); (V.A.); (G.M.); (A.L.); (N.R.); (F.P.); (S.R.)
| | - Francesco Paoloni
- Department of Medical Oncology, Università Politecnica delle Marche, AOU Ospedali Riuniti Ancona, 60126 Ancona, Italy; (E.L.); (L.C.); (F.P.); (V.C.); (V.A.); (G.M.); (A.L.); (N.R.); (F.P.); (S.R.)
| | - Silvia Rinaldi
- Department of Medical Oncology, Università Politecnica delle Marche, AOU Ospedali Riuniti Ancona, 60126 Ancona, Italy; (E.L.); (L.C.); (F.P.); (V.C.); (V.A.); (G.M.); (A.L.); (N.R.); (F.P.); (S.R.)
| | - Linda Nicolardi
- Medical Oncology, Ospedali Riuniti Padova Sud, 35043 Monselice, Italy; (L.N.); (R.C.)
| | - Andrea Caglio
- Department of Oncology, University of Turin, Ordine Mauriziano Hospital, 10128 Torino, Italy; (A.C.); (M.D.M.)
| | - Sophie Aerts
- Department of Pulmonary Medicine, Erasmus MC Rotterdam, 3015 GD Rotterdam, The Netherlands; (S.A.); (A.-M.C.D.); (J.G.J.V.A.)
- Erasmus MC Cancer Institute, Erasmus MC Rotterdam, 3015 GD Rotterdam, The Netherlands
| | - Alessio Cortellini
- Medical Oncology, St Salvatore Hospital, 67100 L’Aquila, Italy; (A.C.); (C.F.)
- Department of Biotechnology and Applied Clinical Sciences, University of L’Aquila, 67100 L’Aquila, Italy
| | - Corrado Ficorella
- Medical Oncology, St Salvatore Hospital, 67100 L’Aquila, Italy; (A.C.); (C.F.)
- Department of Biotechnology and Applied Clinical Sciences, University of L’Aquila, 67100 L’Aquila, Italy
| | - Rita Chiari
- Medical Oncology, Ospedali Riuniti Padova Sud, 35043 Monselice, Italy; (L.N.); (R.C.)
| | - Massimo Di Maio
- Department of Oncology, University of Turin, Ordine Mauriziano Hospital, 10128 Torino, Italy; (A.C.); (M.D.M.)
| | - Anne-Marie C. Dingemans
- Department of Pulmonary Medicine, Erasmus MC Rotterdam, 3015 GD Rotterdam, The Netherlands; (S.A.); (A.-M.C.D.); (J.G.J.V.A.)
- Erasmus MC Cancer Institute, Erasmus MC Rotterdam, 3015 GD Rotterdam, The Netherlands
| | - Joachim G. J. V. Aerts
- Department of Pulmonary Medicine, Erasmus MC Rotterdam, 3015 GD Rotterdam, The Netherlands; (S.A.); (A.-M.C.D.); (J.G.J.V.A.)
- Erasmus MC Cancer Institute, Erasmus MC Rotterdam, 3015 GD Rotterdam, The Netherlands
| | - Rossana Berardi
- Department of Medical Oncology, Università Politecnica delle Marche, AOU Ospedali Riuniti Ancona, 60126 Ancona, Italy; (E.L.); (L.C.); (F.P.); (V.C.); (V.A.); (G.M.); (A.L.); (N.R.); (F.P.); (S.R.)
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SchnÖller L, KÄsmann L, Taugner J, Abdo R, Eze C, Manapov F. Prognostic Role of Lung Immune Scores for Prediction of Survival in Limited-stage Small Cell Lung Cancer. In Vivo 2021; 35:929-935. [PMID: 33622885 PMCID: PMC8045058 DOI: 10.21873/invivo.12333] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2020] [Revised: 12/10/2020] [Accepted: 12/21/2020] [Indexed: 12/31/2022]
Abstract
BACKGROUND/AIM Previous studies have suggested the prognostic value of the Lung Immune Prediction Index (LIPI) and the Gustave Roussy Score (GRIM) as prognostic markers in advanced small cell lung cancer (SCLC). However, LIPI and GRIM score have not been evaluated in patients with limited stage SCLC (LS-SCLC). PATIENTS AND METHODS Pretreatment LIPI and GRIM score of 33 (43%) patients out of 77 LS-SCLC patients treated with chemoradiotherapy (CRT) during 2004-2015 were included. RESULTS The median overall survival (OS) time in the good, intermediate, and poor LIPI subgroups were 14, 17 and 3 months (p=0.973) and 14, 17 and 17 months in the GRIM subgroups. In univariate analysis, patients age <65 years (p=0.008), concurrent chemotherapy (p=0.028), and administering prophylactic cranial irradiation (PCI) (p=0.031) were associated with improved OS. Using Cox regression analysis, age remained significant (HR=3.299, p=0.031) and PCI showed a trend (HR=2.801, p=0.06). CONCLUSION Independent predictors of overall survival were identified and can contribute to improved treatment personalization. Concurrent chemotherapy and PCI after CRT were associated with improved OS compared to LIPI- and GRIM-score, which had no prognostic impact in LS-SCLC.
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Affiliation(s)
- Leon SchnÖller
- Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany
| | - Lukas KÄsmann
- Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany;
- Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research (DZL), Munich, Germany
- German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany
| | - Julian Taugner
- Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany
| | - Reem Abdo
- Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany
| | - Chukwuka Eze
- Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany
| | - Farkhad Manapov
- Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany
- Comprehensive Pneumology Center Munich (CPC-M), Member of the German Center for Lung Research (DZL), Munich, Germany
- German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany
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Gustave Roussy Immune Score based on a three-category risk assessment scale serves as a novel and effective prognostic indicator for surgically resectable early-stage non-small-cell lung cancer: A propensity score matching retrospective cohort study. Int J Surg 2020; 84:25-40. [DOI: 10.1016/j.ijsu.2020.10.015] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Accepted: 10/13/2020] [Indexed: 02/07/2023]
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Sun R, Sundahl N, Hecht M, Putz F, Lancia A, Rouyar A, Milic M, Carré A, Battistella E, Alvarez Andres E, Niyoteka S, Romano E, Louvel G, Durand-Labrunie J, Bockel S, Bahleda R, Robert C, Boutros C, Vakalopoulou M, Paragios N, Frey B, Soria JC, Massard C, Ferté C, Fietkau R, Ost P, Gaipl U, Deutsch E. Radiomics to predict outcomes and abscopal response of patients with cancer treated with immunotherapy combined with radiotherapy using a validated signature of CD8 cells. J Immunother Cancer 2020; 8:jitc-2020-001429. [PMID: 33188037 PMCID: PMC7668366 DOI: 10.1136/jitc-2020-001429] [Citation(s) in RCA: 48] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/29/2020] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Combining radiotherapy (RT) with immuno-oncology (IO) therapy (IORT) may enhance IO-induced antitumor response. Quantitative imaging biomarkers can be used to provide prognosis, predict tumor response in a non-invasive fashion and improve patient selection for IORT. A biologically inspired CD8 T-cells-associated radiomics signature has been developed on previous cohorts. We evaluated here whether this CD8 radiomic signature is associated with lesion response, whether it may help to assess disease spatial heterogeneity for predicting outcomes of patients treated with IORT. We also evaluated differences between irradiated and non-irradiated lesions. METHODS Clinical data from patients with advanced solid tumors in six independent clinical studies of IORT were investigated. Immunotherapy consisted of 4 different drugs (antiprogrammed death-ligand 1 or anticytotoxic T-lymphocyte-associated protein 4 in monotherapy). Most patients received stereotactic RT to one lesion. Irradiated and non-irradiated lesions were delineated from baseline and the first evaluation CT scans. Radiomic features were extracted from contrast-enhanced CT images and the CD8 radiomics signature was applied. A responding lesion was defined by a decrease in lesion size of at least 30%. Dispersion metrices of the radiomics signature were estimated to evaluate the impact of tumor heterogeneity in patient's response. RESULTS A total of 94 patients involving multiple lesions (100 irradiated and 189 non-irradiated lesions) were considered for a statistical interpretation. Lesions with high CD8 radiomics score at baseline were associated with significantly higher tumor response (area under the receiving operating characteristic curve (AUC)=0.63, p=0.0020). Entropy of the radiomics scores distribution on all lesions was shown to be associated with progression-free survival (HR=1.67, p=0.040), out-of-field abscopal response (AUC=0.70, p=0.014) and overall survival (HR=2.08, p=0.023), which remained significant in a multivariate analysis including clinical and biological variables. CONCLUSIONS These results enhance the predictive value of the biologically inspired CD8 radiomics score and suggests that tumor heterogeneity should be systematically considered in patients treated with IORT. This CD8 radiomics signature may help select patients who are most likely to benefit from IORT.
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Affiliation(s)
- Roger Sun
- Department of Radiation Oncology, Gustave Roussy, Villejuif, Île-de-France, France.,Institut Gustave Roussy, Inserm, Radiothérapie Moléculaire et Innovation Thérapeutique, Paris-Saclay University, Villejuif, Île-de-France, France.,Paris-Saclay University Faculty of Medicine, Le Kremlin-Bicetre, Île-de-France, France
| | - Nora Sundahl
- Department of Radiation Oncology, University Hospital Ghent, Gent, Oost-Vlaanderen, Belgium
| | - Markus Hecht
- Department of Radiation Oncology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Florian Putz
- Department of Radiation Oncology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Andrea Lancia
- Department of Radiation Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Lombardia, Italy
| | - Angela Rouyar
- Institut Gustave Roussy, Inserm, Radiothérapie Moléculaire et Innovation Thérapeutique, Paris-Saclay University, Villejuif, Île-de-France, France
| | - Marina Milic
- Institut Gustave Roussy, Inserm, Radiothérapie Moléculaire et Innovation Thérapeutique, Paris-Saclay University, Villejuif, Île-de-France, France
| | - Alexandre Carré
- Department of Radiation Oncology, Gustave Roussy, Villejuif, Île-de-France, France.,Institut Gustave Roussy, Inserm, Radiothérapie Moléculaire et Innovation Thérapeutique, Paris-Saclay University, Villejuif, Île-de-France, France
| | - Enzo Battistella
- Institut Gustave Roussy, Inserm, Radiothérapie Moléculaire et Innovation Thérapeutique, Paris-Saclay University, Villejuif, Île-de-France, France
| | - Emilie Alvarez Andres
- Institut Gustave Roussy, Inserm, Radiothérapie Moléculaire et Innovation Thérapeutique, Paris-Saclay University, Villejuif, Île-de-France, France.,TheraPanacea, Paris, France
| | - Stéphane Niyoteka
- Institut Gustave Roussy, Inserm, Radiothérapie Moléculaire et Innovation Thérapeutique, Paris-Saclay University, Villejuif, Île-de-France, France
| | - Edouard Romano
- Department of Radiation Oncology, Gustave Roussy, Villejuif, Île-de-France, France
| | - Guillaume Louvel
- Department of Radiation Oncology, Gustave Roussy, Villejuif, Île-de-France, France
| | | | - Sophie Bockel
- Department of Radiation Oncology, Gustave Roussy, Villejuif, Île-de-France, France.,Institut Gustave Roussy, Inserm, Radiothérapie Moléculaire et Innovation Thérapeutique, Paris-Saclay University, Villejuif, Île-de-France, France.,Paris-Saclay University Faculty of Medicine, Le Kremlin-Bicetre, Île-de-France, France
| | - Rastilav Bahleda
- Drug Development Department, Gustave Roussy, Villejuif, Île-de-France, France
| | - Charlotte Robert
- Department of Radiation Oncology, Gustave Roussy, Villejuif, Île-de-France, France.,Institut Gustave Roussy, Inserm, Radiothérapie Moléculaire et Innovation Thérapeutique, Paris-Saclay University, Villejuif, Île-de-France, France
| | - Celine Boutros
- Departement of Medicine, Gustave Roussy, Villejuif, Île-de-France, France
| | | | - Nikos Paragios
- TheraPanacea, Paris, France.,CentraleSupélec, Gif-sur-Yvette, Île-de-France, France
| | - Benjamin Frey
- Department of Radiation Oncology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Jean-Charles Soria
- Departement of Medicine, Gustave Roussy, Villejuif, Île-de-France, France
| | - Christophe Massard
- Paris-Saclay University Faculty of Medicine, Le Kremlin-Bicetre, Île-de-France, France.,Drug Development Department, Gustave Roussy, Villejuif, Île-de-France, France
| | - Charles Ferté
- Departement of Medicine, Gustave Roussy, Villejuif, Île-de-France, France
| | - Rainer Fietkau
- Department of Radiation Oncology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Piet Ost
- Department of Radiation Oncology, University Hospital Ghent, Gent, Oost-Vlaanderen, Belgium
| | - Udo Gaipl
- Department of Radiation Oncology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - Eric Deutsch
- Department of Radiation Oncology, Gustave Roussy, Villejuif, Île-de-France, France .,Institut Gustave Roussy, Inserm, Radiothérapie Moléculaire et Innovation Thérapeutique, Paris-Saclay University, Villejuif, Île-de-France, France.,Paris-Saclay University Faculty of Medicine, Le Kremlin-Bicetre, Île-de-France, France
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Minami S, Ihara S, Komuta K. Sarcopenia and Visceral Adiposity Are Not Independent Prognostic Markers for Extensive Disease of Small-Cell Lung Cancer: A Single-Centered Retrospective Cohort Study. World J Oncol 2020; 11:139-149. [PMID: 32849954 PMCID: PMC7430857 DOI: 10.14740/wjon1289] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2020] [Accepted: 06/04/2020] [Indexed: 12/25/2022] Open
Abstract
Background Sarcopenia and visceral adiposity have been suggested to affect prognosis and treatment efficacy in various types of cancers. The aim of our study was to evaluate whether pretreatment sarcopenia and visceral adiposity are associated with prognosis in patients with extensive-disease small-cell lung cancer (ED-SCLC). Methods Between September 2007 and March 2018, 128 ED-SCLC patients received first-line and platinum-based chemotherapy at our hospital. Based on pretreatment body mass index (BMI), psoas muscle index (PMI), intramuscular adipose tissue content (IMAC) and visceral-to-subcutaneous fat ratio (VSR) at lumbar vertebra L3 level, we divided these patients into two groups, and then compared overall survival (OS) and progression-free survival (PFS). Adjusted by age, serum albumin, lactate dehydrogenase (LDH), clinical stage and performance status, we detected independent prognostic factors by multivariate Cox proportional hazard analyses. Results We did not find any significant differences in OS and PFS between two groups divided by BMI, PMI, IMAC and VSR. According to multivariate analyses, none of BMI, PMI, IMAC and VSR was an independent prognostic factor of OS and PFS. Conclusions Neither pretreatment sarcopenia nor visceral adiposity is a prognostic marker of patients with ED-SCLC treated with standard regimen of platinum-based chemotherapy.
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Affiliation(s)
- Seigo Minami
- Department of Respiratory Medicine, Osaka Police Hospital, 10-31 Kitayama-cho, Tennoji-ku, Osaka 543-0035, Japan.,Department of Respiratory Medicine, Daini Osaka Police Hospital, 2-6-40 Karasugatsuji, Tennoji-ku, Osaka 543-8922, Japan
| | - Shoichi Ihara
- Department of Respiratory Medicine, Osaka Police Hospital, 10-31 Kitayama-cho, Tennoji-ku, Osaka 543-0035, Japan.,Department of Respiratory Medicine, Daini Osaka Police Hospital, 2-6-40 Karasugatsuji, Tennoji-ku, Osaka 543-8922, Japan
| | - Kiyoshi Komuta
- Department of Respiratory Medicine, Daini Osaka Police Hospital, 2-6-40 Karasugatsuji, Tennoji-ku, Osaka 543-8922, Japan
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Huang Y, Shen A. The prediction potential of neutrophil-to-lymphocyte ratio for the therapeutic outcomes of programmed death receptor-1/programmed death ligand 1 inhibitors in non-small cell lung cancer patients: A meta-analysis. Medicine (Baltimore) 2020; 99:e21718. [PMID: 32846790 PMCID: PMC7447402 DOI: 10.1097/md.0000000000021718] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Programmed death receptor-1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors have been demonstrated to improve the prognosis of patients with advanced non-small cell lung cancer (NSCLC) compared with chemotherapy. However, there were still some non-responders. Thus, how to effectively screen the responder may be an important issue. Recent studies revealed the immune-related indicator, neutrophil-lymphocyte ratio (NLR), may predict the therapeutic effects of anti-PD1/PD-L1 antibodies; however, the results were controversial. This study was to re-evaluate the prognostic potential of NLR for NSCLC patients receiving PD1/PD-L1 inhibitors by performing a meta-analysis. METHODS Eligible studies were identified by searching online databases of PubMed, EMBASE and Cochrane Library. The predictive values of NLR for overall survival, (OS), progression free survival (PFS) and overall response rate (ORR) were estimated by hazard ratio (HR) with 95% confidence interval (CI). RESULTS Twenty-four studies involving 2196 patients were included. The pooled analysis demonstrated that elevated NLR before PD-1/PD-L1 inhibitor treatment was a predictor of poor OS (HR = 2.17; 95% CI: 1.64 - 2.87, P < .001), PFS (HR = 1.54; 95% CI: 1.34 - 1.78, P < .001) and low ORR (HR = 0.64; 95% CI: 0.44 - 0.95, P = .027) in NSCLC patients. Subgroup analysis revealed the predictive ability of NLR for OS and PFS was not changed by ethnicity, sample size, cut-off, HR source, study design or inhibitor type (except the combined anti-PD-L1 group); while its association with ORR was only significant when the cut-off value was less than 5 and the studies were prospectively designed. CONCLUSION Our findings suggest patients with lower NLR may benefit from the use of PD-1/PD-L1 inhibitors to prolong their survival period.
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Jin J, Yang L, Liu D, Li W. Association of the neutrophil to lymphocyte ratio and clinical outcomes in patients with lung cancer receiving immunotherapy: a meta-analysis. BMJ Open 2020; 10:e035031. [PMID: 32499266 PMCID: PMC7282333 DOI: 10.1136/bmjopen-2019-035031] [Citation(s) in RCA: 67] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
OBJECTIVES To explore the relationship between the pretreatment or post-treatment neutrophil to lymphocyte ratio (NLR) and overall survival (OS)/progression-free survival (PFS) in patients with lung cancer receiving immunotherapy. DESIGN We searched several databases to collect relevant studies conducted until July 2019. We carefully reviewed the full text of the included publications and combined the HRs and 95% CIs to assess the association between the NLR and survival time in patients with lung cancer receiving immunotherapy. DATA SOURCES PubMed, the Cochrane Library, Embase and Web of Science ELIGIBILITY CRITERIA: Studies reporting the prognostic value of the NLR in patients with lung cancer receiving immunotherapy were enrolled. DATA EXTRACTION AND SYNTHESIS Basic information on the articles and patients (NLR cut-off value, NLR at baseline and HRs with 95% CIs for OS and PFS) was extracted by two authors independently. The pooled HRs of OS and PFS were synthesised using the random effects or fixed effects model. RESULTS Twenty-three studies with 2068 patients were enrolled. Among all patients, 1305 (64.0%) were men and 643 (31.4%) were diagnosed with squamous cell carcinoma (SCC). In a pooled analysis of OS and PFS from all studies, an elevated NLR predicted poor OS (HR=1.62; 95% CI: 1.41 to 1.87; p<0.001) and PFS (HR=1.47; 95% CI: 1.25 to 1.72; p<0.001). Subgroup analyses stratified showed that the post-treatment NLR was not significantly related to OS and that patients in Asia had significantly higher HRs than those in Europe and America. Furthermore, the proportion of SCC and baseline NLR could affect the prognostic value of the NLR. CONCLUSIONS Our study found that an elevated NLR was associated with poor OS and PFS in patients with lung cancer receiving immunotherapy and that several clinical factors might have an impact on the predictive value of the NLR in the survival of patients with lung cancer.
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Affiliation(s)
- Jing Jin
- Department of Respiratory & Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Lan Yang
- Department of Respiratory & Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Dan Liu
- Department of Respiratory & Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Weimin Li
- Department of Respiratory & Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, China
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Minami S, Ihara S, Komuta K. Gustave Roussy Immune Score and Royal Marsden Hospital Prognostic Score Are Prognostic Markers for Extensive Disease of Small Cell Lung Cancer. World J Oncol 2020; 11:98-105. [PMID: 32494316 PMCID: PMC7239571 DOI: 10.14740/wjon1275] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2020] [Accepted: 04/01/2020] [Indexed: 01/28/2023] Open
Abstract
Background The Royal Marsden Hospital prognostic score (RMH score) and the Gustave Roussy immune score (GRIm-score) were developed in order to select more suitable patient for phase I trials. Lactate dehydrogenase (LDH) and serum albumin concentration are common risk factors to these two systems. As the third risk factor, the RMH score and the GRIm-score adopt number of metastatic sites and neutrophil-to-lymphocyte ratio (NLR), respectively. We aimed to investigate whether these two systems are also useful for extensive disease of small cell lung cancer (ED-SCLC). Methods We retrospectively collected 128 patients who had initiated platinum-based chemotherapy at our hospital between September 2007 and March 2018. We divided our patients into low (score 0 - 1) and high (2 - 3) score groups, and compared overall survival (OS) and progression-free survival (PFS) between them. Multivariate Cox proportional hazard analyses found prognostic factors of survival times. Results Regarding GRIm-score, OS was significantly shorter in high score group than in low score group (median 6.1 vs. 11.4 months, P < 0.01), while no significant difference was observed in PFS (median 4.7 vs. 5.0 months, P = 0.12). Both OS (median 6.9 vs. 12.4 months, P < 0.01) and PFS (median 4.4 vs. 5.4 months, P = 0.01) were significantly shorter in high RMH score group than in low group. Multivariate analyses detected both high GRIm-score (hazard ratio (HR) 1.80, 95% confidence interval (CI) 1.20 - 2.72, P < 0.01) and high RMH score (HR 1.93, 95% CI 1.27 - 2.92, P < 0.01) as independent worse prognostic factors of OS, and then only high RMH score (HR 1.53, 95% CI 1.04 - 2.25, P = 0.03) as independent worse prognostic factor of PFS. Conclusions Both RMH score and GRIm-score are useful as independent prognostic factors of OS in ED-SCLC. However, only RMH score is an independent prognostic factor of PFS.
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Affiliation(s)
- Seigo Minami
- Department of Respiratory Medicine, Osaka Police Hospital, 10-31 Kitayama-cho, Tennoji-ku, Osaka 543-0035, Japan.,Department of Respiratory Medicine, Daini Osaka Police Hospital, 2-6-40 Karasugatsuji, Tennoji-ku, Osaka 543-8922, Japan
| | - Shouichi Ihara
- Department of Respiratory Medicine, Osaka Police Hospital, 10-31 Kitayama-cho, Tennoji-ku, Osaka 543-0035, Japan
| | - Kiyoshi Komuta
- Department of Respiratory Medicine, Daini Osaka Police Hospital, 2-6-40 Karasugatsuji, Tennoji-ku, Osaka 543-8922, Japan
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Hopkins AM, Kichenadasse G, Garrett-Mayer E, Karapetis CS, Rowland A, Sorich MJ. Development and Validation of a Prognostic Model for Patients with Advanced Lung Cancer Treated with the Immune Checkpoint Inhibitor Atezolizumab. Clin Cancer Res 2020; 26:3280-3286. [PMID: 32086341 DOI: 10.1158/1078-0432.ccr-19-2968] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2019] [Revised: 12/17/2019] [Accepted: 02/16/2020] [Indexed: 11/16/2022]
Abstract
PURPOSE Immune checkpoint inhibitors (ICI) are a significant advance to the treatment of advanced non-small cell lung cancer (NSCLC); however, their initiation is associated with heterogeneity in outcomes. This study aimed to develop and validate a prognostic tool of survival in patients with advanced NSCLC treated with ICIs. EXPERIMENTAL DESIGN A pretreatment prognostic model was developed and validated using clinicopathologic data. Development data consisted of patients with advanced NSCLC treated with atezolizumab from the randomised trials OAK and POPLAR (n = 751). Data from the single-arm atezolizumab trials BIRCH and FIR (n = 797) were used for external validation. Prognostic scores were categorized into low, intermediate-low, intermediate, intermediate-high, and high-risk prognostic groups. The primary outcome was overall survival (OS), with progression-free survival (PFS) secondary. RESULTS Pretreatment C-reactive protein (CRP) was the most predictive variable for OS. The prognostic tool was optimally defined by CRP, lactate dehydrogenase, derived neutrophil-to-lymphocyte ratio, albumin, PD-L1 expression, performance status, time since metastatic diagnosis, and metastatic site count. Prognostic groups had significantly different OS (c-statistic = 0.72), with median OS ranging from >24 to 3 months for the low- to high-risk groups. Performance was maintained on validation (c = 0.76). These findings were similar for PFS, with median PFS ranging from 5 months to 1 month for the low- to high-risk groups. Benefit of atezolizumab (vs. docetaxel) was greatest in the low-risk group (>3 months median OS improvement), with little benefit apparent for the highest risk group. CONCLUSIONS A prognostic tool was developed and validated to identify patient groups with distinctly different survival following atezolizumab initiation for advanced NSCLC.
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Affiliation(s)
- Ashley M Hopkins
- College of Medicine and Public Health, Flinders University, Adelaide, Australia.
| | - Ganessan Kichenadasse
- College of Medicine and Public Health, Flinders University, Adelaide, Australia.,Department of Medical Oncology, Flinders Medical Centre, Adelaide, Australia
| | | | - Christos S Karapetis
- College of Medicine and Public Health, Flinders University, Adelaide, Australia.,Department of Medical Oncology, Flinders Medical Centre, Adelaide, Australia
| | - Andrew Rowland
- College of Medicine and Public Health, Flinders University, Adelaide, Australia
| | - Michael J Sorich
- College of Medicine and Public Health, Flinders University, Adelaide, Australia
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Feng JF, Wang L, Yang X, Chen S. Gustave Roussy Immune Score (GRIm-Score) is a prognostic marker in patients with resectable esophageal squamous cell carcinoma. J Cancer 2020; 11:1334-1340. [PMID: 32047540 PMCID: PMC6995395 DOI: 10.7150/jca.37898] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2019] [Accepted: 11/20/2019] [Indexed: 12/17/2022] Open
Abstract
Background: The Gustave Roussy Immune Score (GRIm-Score) was initially reported to select patients for immunotherapy. Therefore, the purpose of the current retrospective study was to determine whether GRIm-Score, a novel nutritional and inflammatory-based prognostic score, is a useful prognostic marker in patients with esophageal squamous cell carcinoma (ESCC) undergoing surgical resection. Methods: A retrospective single institutional study including 372 ESCC patients undergoing surgical resection was performed. The GRIm-Score was simply calculated by lactate dehydrogenase (LDH), neutrophil lymphocyte ratio (NLR) and albumin (ALB). The cancer-specific survival (CSS) was analyzed for the current study with Cox regression analyses with forward stepwise and Kaplan-Meier methods. Results: There were 284 (76.3%) men and 88 (23.7%) women with the mean age of 59.3 ± 8.0 years (range: 36-80 years). Patient with a high GRIm-Score had poor CSS (10.3% vs. 35.0%, P < 0.001). The GRIm-Score, in multivariate analyses, instead of NLR, LDH or ALB, was an independent prognostic factor for CSS (P = 0.004). Conclusion: The GRIm-Score was an independent prognostic marker in patients with ESCC undergoing surgical resection. Our study is also the first study to discuss the prognostic value of GRIm-Score in patients with resectable ESCC.
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Affiliation(s)
- Ji-Feng Feng
- Department of Thoracic Oncological Surgery, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, No.38 Guangji Road, Hangzhou 310022, China
- Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology, No.38 Guangji Road, Zhejiang province, Hangzhou 310022, China
| | - Liang Wang
- Department of Thoracic Oncological Surgery, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, No.38 Guangji Road, Hangzhou 310022, China
| | - Xun Yang
- Department of Thoracic Oncological Surgery, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, No.38 Guangji Road, Hangzhou 310022, China
- Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology, No.38 Guangji Road, Zhejiang province, Hangzhou 310022, China
| | - Sheng Chen
- Department of Thoracic Oncological Surgery, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, No.38 Guangji Road, Hangzhou 310022, China
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