Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Clinical Studies

Systemic inflammatory prognostic scores in advanced pancreatic adenocarcinoma

British Journal of Cancer (2023)Cite this article

Subjects

Abstract

Background

Systemic inflammatory scores may aid prognostication and patient selection for trials. We compared five scores in advanced pancreatic adenocarcinoma (PDAC).

Methods

Unresectable/metastatic PDAC patients enrolled in the Comprehensive Molecular Characterisation of Advanced Pancreatic Ductal Adenocarcinoma for Better Treatment Selection trial (NCT02750657) were included. Patients had pre-treatment biopsies for whole genome and RNA sequencing. CD8 immunohistochemistry was available in a subset. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, Prognostic Nutritional Index, Gustave Roussy Immune Score (GRIm-S), and Memorial Sloan Kettering Prognostic Score (MPS) were calculated. Overall survival (OS) was estimated using Kaplan–Meier methods. Associations between inflammatory scores, clinical/genomic characteristics, and OS were analysed.

Results

We analysed 263 patients. High-risk NLR, GRIm-S and MPS were poorly prognostic. The GRIm-S had the highest predictive ability: median OS 6.4 vs. 10 months for high risk vs. low-risk (P < 0.001); HR 2.26 (P < 0.001). ECOG ≥ 1, the basal-like subtype, and low-HRDetect were additional poor prognostic factors (P < 0.01). Inflammatory scores did not associate with RNA-based classifiers or homologous recombination repair deficiency genotypes. High-risk MPS (P = 0.04) and GRIm-S (P = 0.02) patients had lower median CD8 + tumour-infiltrating lymphocytes.

Conclusions

Inflammatory scores incorporating NLR have prognostic value in advanced PDAC. Understanding immunophenotypes of poor-risk patients and using these scores in trials will advance the field.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Get just this article for as long as you need it

$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Oncoprint showing genomic features of cases enrolled on the COMPASS trial.
Fig. 2: Kaplan–Meier survival curves.

Data availability

All RNA sequencing data have been deposited in the European Genome-Phenome Archive (EGA) at EGAD00001009409.

References

  1. Conroy T, Desseigne F, Ychou M, Bouche O, Guimbaud R, Becouarn Y, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364:1817–25.

    Article  CAS  PubMed  Google Scholar 

  2. Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369:1691–703.

    Article  Google Scholar 

  3. Buzby GP, Mullen JL, Matthews DC, Hobbs CL, Rosato EF. Prognostic nutritional index in gastrointestinal surgery. Am J Surg. 1980;139:160–7.

    Article  CAS  PubMed  Google Scholar 

  4. Onodera T, Goseki N, Kosaki G. Prognostic nutritional index in gastrointestinal surgery of malnourished cancer patients. Nihon Geka Gakkai Zasshi. 1984;85:1001–5.

    CAS  PubMed  Google Scholar 

  5. Forrest LM, McMillan DC, McArdle CS, Angerson WJ, Dunlop DJ. Evaluation of cumulative prognostic scores based on the systemic inflammatory response in patients with inoperable non-small-cell lung cancer. Br J Cancer. 2003;89:1028–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Templeton AJ, Ace O, McNamara MG, Al-Mubarak M, Vera-Badillo FE, Hermanns T, et al. Prognostic role of platelet to lymphocyte ratio in solid tumors: a systematic review and meta-analysis. Cancer Epidemiol Biomark Prev. 2014;23:1204–12.

    Article  CAS  Google Scholar 

  7. Templeton AJ, McNamara MG, Seruga B, Vera-Badillo FE, Aneja P, Ocana A, et al. Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J Natl Cancer Inst. 2014;106:dju124.

    Article  PubMed  Google Scholar 

  8. Bigot F, Castanon E, Baldini C, Hollebecque A, Carmona A, Postel-Vinay S, et al. Prospective validation of a prognostic score for patients in immunotherapy phase I trials: the Gustave Roussy Immune Score (GRIm-Score). Eur J Cancer. 2017;84:212–8.

    Article  CAS  PubMed  Google Scholar 

  9. Lebenthal JM, Zheng J, Glare PA, O’Reilly EM, Yang AC, Epstein AS. Prognostic value of the Memorial Sloan Kettering Prognostic Score in metastatic pancreatic adenocarcinoma. Cancer. 2021;127:1568–75.

    Article  CAS  PubMed  Google Scholar 

  10. Aung KL, Fischer SE, Denroche RE, Jang GH, Dodd A, Creighton S, et al. Genomics-driven precision medicine for advanced pancreatic cancer: early results from the COMPASS trial. Clin Cancer Res. 2018;24:1344–54.

    Article  CAS  PubMed  Google Scholar 

  11. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47.

    Article  CAS  PubMed  Google Scholar 

  12. Moffitt RA, Marayati R, Flate EL, Volmar KE, Loeza SG, Hoadley KA, et al. Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma. Nat Genet. 2015;47:1168–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. O’Kane GM, Grunwald BT, Jang GH, Masoomian M, Picardo S, Grant RC, et al. GATA6 expression distinguishes classical and basal-like subtypes in advanced pancreatic cancer. Clin Cancer Res. 2020;26:4901–10.

    Article  PubMed  Google Scholar 

  14. Davies H, Glodzik D, Morganella S, Yates LR, Staaf J, Zou X, et al. HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures. Nat Med. 2017;23:517–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Harrell FE Jr, Lee KL, Mark DB. Multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors. Stat Med. 1996;15:361–87.

    Article  PubMed  Google Scholar 

  16. Royal RE, Levy C, Turner K, Mathur A, Hughes M, Kammula US, et al. Phase 2 trial of single agent Ipilimumab (anti-CTLA-4) for locally advanced or metastatic pancreatic adenocarcinoma. J Immunother. 2010;33:828–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. O’Reilly EM, Oh DY, Dhani N, Renouf DJ, Lee MA, Sun W, et al. Durvalumab with or without tremelimumab for patients with metastatic pancreatic ductal adenocarcinoma: a phase 2 randomized clinical trial. JAMA Oncol. 2019;5:1431–8.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Kamath SD, Kalyan A, Kircher S, Nimeiri H, Fought AJ, Benson A 3rd, et al. Ipilimumab and gemcitabine for advanced pancreatic cancer: a phase Ib study. Oncologist. 2020;25:e808–e15.

    Article  CAS  PubMed  Google Scholar 

  19. Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell. 2010;140:883–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. McMillan DC. An inflammation-based prognostic score and its role in the nutrition-based management of patients with cancer. Proc Nutr Soc. 2008;67:257–62.

    Article  PubMed  Google Scholar 

  21. Imaoka H, Mizuno N, Hara K, Hijioka S, Tajika M, Tanaka T, et al. Evaluation of modified Glasgow prognostic score for pancreatic cancer: a retrospective cohort study. Pancreas. 2016;45:211–7.

    Article  PubMed  Google Scholar 

  22. Yang JJ, Hu ZG, Shi WX, Deng T, He SQ, Yuan SG. Prognostic significance of neutrophil to lymphocyte ratio in pancreatic cancer: a meta-analysis. World J Gastroenterol. 2015;21:2807–15.

    Article  PubMed  PubMed Central  Google Scholar 

  23. O’Kane GM, Denroche R, Picardo SL, Zhang A, Holter S, Grant RC, et al. Homologous recombination deficiency (HRD) scoring in pancreatic ductal adenocarcinoma (PDAC) and response to chemotherapy. J Clin Oncol. 2020;38:741.

    Article  Google Scholar 

Download references

Acknowledgements

This study was conducted with the support of the Ontario Institute for Cancer Research (PanCuRx Translational Research Initiative) through funding provided by the Government of Ontario, the Wallace McCain Centre for Pancreatic Cancer supported by the Princess Margaret Cancer Foundation, Pancreatic Cancer Canada, the Terry Fox Research Institute, and the Canadian Cancer Society Research Institute.

Funding

This study was funded by the Ontario Institute for Cancer Research (PanCuRx Translational Research Initiative), the Princess Margaret Cancer Foundation, Pancreatic Cancer Canada, a Canadian Cancer Society Research Institute grant (702316), and charitable donations from the Canadian Friends of the Hebrew University (Alex U. Soyka) and the Lebovic Chair in Hepatobiliary/Pancreatic Surgical Oncology.

Author information

Authors and Affiliations

  1. Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada

    Lucy X. Ma, Michael J. Allen, Anna Dodd, Stephanie Ramotar, Shawn Hutchinson, Faiyaz Notta, Steven Gallinger, Robert C. Grant, Rama Khokha, Nathan Chan, Barbara T. Grünwald, Jennifer J. Knox & Grainne M. O’Kane

  2. Research Institute of the McGill University Health Centre; Rosalind and Morris Goodman Cancer Institute, McGill University; Department of Surgery, McGill University, Montreal, QC, Canada

    Yifan Wang & George Zogopoulos

  3. Department of Epidemiology and Biostatistics, Western University, London, ON, Canada

    Osvaldo Espin-Garcia

  4. Dalla Lana School of Public Health & Department of Statistical Sciences, University of Toronto, Toronto, ON, Canada

    Osvaldo Espin-Garcia

  5. Department of Biostatistics, University Health Network, Toronto, ON, Canada

    Osvaldo Espin-Garcia

  6. PanCuRx Ontario Institute for Cancer Research, Toronto, ON, Canada

    Gun Ho Jang, Amy Zhang, Julie M. Wilson, Faiyaz Notta, Steven Gallinger, Robert C. Grant, Jennifer J. Knox & Grainne M. O’Kane

  7. Centre Hospitalier de l’Université de Montréal, Montreal, QC, Canada

    Mustapha Tehfe

  8. QEII Health Sciences Centre, Division of Medical Oncology, Dalhousie University, Halifax, NS, Canada

    Ravi Ramjeesingh

  9. Queen’s University, Kingston, ON, Canada

    James Biagi

  10. Department of Pathology, University Health Network, Toronto, ON, Canada

    Sandra E. Fischer

  11. Hepatobiliary/Pancreatic Surgical Oncology Program, University Health Network, Toronto, ON, Canada

    Steven Gallinger

Authors
  1. Lucy X. Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yifan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Osvaldo Espin-Garcia
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Michael J. Allen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gun Ho Jang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Amy Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Anna Dodd
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Stephanie Ramotar
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Shawn Hutchinson
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Mustapha Tehfe
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Ravi Ramjeesingh
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. James Biagi
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Julie M. Wilson
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Faiyaz Notta
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Sandra E. Fischer
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. George Zogopoulos
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Steven Gallinger
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Robert C. Grant
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Rama Khokha
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Nathan Chan
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Barbara T. Grünwald
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Jennifer J. Knox
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. Grainne M. O’Kane
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

LXM: conceptualisation, data curation, investigation and writing (original draft, review and editing). YW: data curation, investigation and writing (original draft, review and editing). OE-G: formal analysis and writing (review and editing). MJA: data curation, investigation and writing (original draft, review and editing). GHJ: data curation, investigation and writing (original draft, review and editing). AZ: data curation, investigation and writing (original draft, review and editing). AD: data curation, investigation and writing (original draft, review and editing). SR: data curation, investigation and writing (original draft, review and editing). SH: data curation, investigation and writing (original draft, review and editing). MT: investigation and writing (original draft, review and editing). RR: investigation and writing (original draft, review and editing). JB: investigation and writing (original draft, review and editing). JW: data curation, investigation and writing (original draft, review and editing). FN: data curation, investigation and writing (original draft, review and editing). SEF: data curation, investigation and writing (original draft, review and editing). GZ: investigation and writing (original draft, review and editing). SG: data curation, investigation, resources and funding acquisition and writing (original draft, review and editing). RCG: data curation, investigation and writing (original draft, review and editing). RK: data curation, investigation and writing (review and editing). NC: data curation, investigation and writing (review and editing). BTG: data curation, investigation and writing (review and editing). JJK: data curation, investigation, resources and funding acquisition and writing (original draft, review and editing). GMO’K: conceptualisation, data curation, investigation, resources and funding acquisition and writing (original draft, review and editing). The final manuscript was approved by all authors.

Corresponding author

Correspondence to Grainne M. O’Kane.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

This study was performed in accordance with the Declaration of Helsinki. The study was approved by the University Health Network Research Ethics Board.

Consent for publication

Not applicable.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Ma, L.X., Wang, Y., Espin-Garcia, O. et al. Systemic inflammatory prognostic scores in advanced pancreatic adenocarcinoma. Br J Cancer (2023). https://doi.org/10.1038/s41416-023-02214-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41416-023-02214-0

Search

Advanced search

Quick links