C-Reactive Protein Kinetic As a Potential Predictive and Prognostic Factor During Treatment with Checkpoint Inhibitors in R/M-HNSCC

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2024 Jul 13

PMID 39001486

Authors

Frederic Jungbauer

Claudia Scherl

Nicole Rotter

Annette Affolter

Anne Lammert

Elena Seiz

Margot Thiaucourt

Lena Huber

Affiliations

Soon will be listed here.

Abstract

Introduction The kinetic of C-reactive protein (CRP) in the early phase of therapy with checkpoint inhibitors (CPI) and its prognostic value has already been investigated in several tumor entities. In particular, flare dynamics have been described as a positive prognostic parameter. The aim of this retrospective study is to examine the extent to which such an application can also be transferred to patients with recurrent or metastatic squamous cell carcinoma of the head and neck region (R/M-HNSCC). Material and Methods All patients treated with CPI for R/M-HNSCC at our clinic between 2018 and 2023 were included ( = 44). Demographic, clinical, histopathologic and laboratory data were extracted from the digital patient records and statistically analyzed. We then examined the CRP kinetic using two previously published classifications and proposed a new classification ourselves. Subsequently, correlation analyses were performed with the overall survival (OS) of the patients. Results Of the two CRP kinetic classifications previously published, only one showed a correlation with the result of the first re-staging, and neither showed a correlation with the OS of R/M-HNSCC patients. Our new CRP kinetic classification showed a significant association with OS in R/M-HNSCC patients ( = 0.05). In a multivariate analysis, our CRP kinetic classification ( = 0.007) and the outcome of the first re-staging ( = 0.002) were significant independent factors for OS. Discussion Our novel CRP kinetic classification significantly correlates with OS in R/M-HNSCC patients, indicating a potential prognostic marker. Existing classifications from other cancer entities showed limited prognostic significance, emphasizing the need for tailored markers. For validation, however, testing on larger R/M-HNSCC patient collectives is necessary.

References

Tomisaki I, Harada M, Tokutsu K, Minato A, Nagata Y, Kimuro R . Impact of C-reactive Protein Flare Response in Patients With Advanced Urothelial Carcinoma Who Received Pembrolizumab. In Vivo. 2021; 35(6):3563-3568. PMC: 8627767. DOI: 10.21873/invivo.12659. View

Tanoue K, Tamura S, Kusaba H, Shinohara Y, Ito M, Tsuchihashi K . Predictive impact of C-reactive protein to albumin ratio for recurrent or metastatic head and neck squamous cell carcinoma receiving nivolumab. Sci Rep. 2021; 11(1):2741. PMC: 7854616. DOI: 10.1038/s41598-021-82448-1. View

Tachinami H, Tomihara K, Yamada S, Ikeda A, Imaue S, Hirai H . Neutrophil-to-lymphocyte ratio as an early marker of outcomes in patients with recurrent oral squamous cell carcinoma treated with nivolumab. Br J Oral Maxillofac Surg. 2023; 61(4):320-326. DOI: 10.1016/j.bjoms.2023.03.012. View

Wang D, DuBois R . Immunosuppression associated with chronic inflammation in the tumor microenvironment. Carcinogenesis. 2015; 36(10):1085-93. PMC: 5006153. DOI: 10.1093/carcin/bgv123. View

Ferris R . Immunology and Immunotherapy of Head and Neck Cancer. J Clin Oncol. 2015; 33(29):3293-304. PMC: 4586169. DOI: 10.1200/JCO.2015.61.1509. View

Han Y, Ding Z, Chen B, Liu Y, Liu Y . A Novel Inflammatory Response-Related Gene Signature Improves High-Risk Survival Prediction in Patients With Head and Neck Squamous Cell Carcinoma. Front Genet. 2022; 13:767166. PMC: 9035793. DOI: 10.3389/fgene.2022.767166. View

Fukuda S, Saito K, Yasuda Y, Kijima T, Yoshida S, Yokoyama M . Impact of C-reactive protein flare-response on oncological outcomes in patients with metastatic renal cell carcinoma treated with nivolumab. J Immunother Cancer. 2021; 9(2). PMC: 7896625. DOI: 10.1136/jitc-2020-001564. View

Ko C, Fang K, Hsu C, Lee Y, Chang G, Huang E . The preoperative C-reactive protein-lymphocyte ratio and the prognosis of oral cavity squamous cell carcinoma. Head Neck. 2021; 43(9):2740-2754. DOI: 10.1002/hed.26738. View

Saal J, Bald T, Eckstein M, Ritter M, Brossart P, Ellinger J . Early C-reactive protein kinetics predicts immunotherapy response in non-small cell lung cancer in the phase III OAK trial. JNCI Cancer Spectr. 2023; 7(2). PMC: 10121335. DOI: 10.1093/jncics/pkad027. View

10.

Ferris R, Blumenschein Jr G, Fayette J, Guigay J, Colevas A, Licitra L . Nivolumab vs investigator's choice in recurrent or metastatic squamous cell carcinoma of the head and neck: 2-year long-term survival update of CheckMate 141 with analyses by tumor PD-L1 expression. Oral Oncol. 2018; 81:45-51. PMC: 6563923. DOI: 10.1016/j.oraloncology.2018.04.008. View

11.

Klumper N, Saal J, Berner F, Lichtensteiger C, Wyss N, Heine A . C reactive protein flare predicts response to checkpoint inhibitor treatment in non-small cell lung cancer. J Immunother Cancer. 2022; 10(3). PMC: 8928397. DOI: 10.1136/jitc-2021-004024. View

12.

Klumper N, Schmucker P, Hahn O, Hoh B, Mattigk A, Banek S . C-reactive protein flare-response predicts long-term efficacy to first-line anti-PD-1-based combination therapy in metastatic renal cell carcinoma. Clin Transl Immunology. 2021; 10(12):e1358. PMC: 8648498. DOI: 10.1002/cti2.1358. View

13.

Klumper N, Sikic D, Saal J, Buttner T, Goldschmidt F, Jarczyk J . C-reactive protein flare predicts response to anti-PD-(L)1 immune checkpoint blockade in metastatic urothelial carcinoma. Eur J Cancer. 2022; 167:13-22. DOI: 10.1016/j.ejca.2022.02.022. View

14.

Eisenhauer E, Therasse P, Bogaerts J, Schwartz L, Sargent D, Ford R . New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2008; 45(2):228-47. DOI: 10.1016/j.ejca.2008.10.026. View

15.

Ohsawa M, Okayama A, Nakamura M, Onoda T, Kato K, Itai K . CRP levels are elevated in smokers but unrelated to the number of cigarettes and are decreased by long-term smoking cessation in male smokers. Prev Med. 2005; 41(2):651-6. DOI: 10.1016/j.ypmed.2005.02.002. View

16.

Ishihara H, Takagi T, Kondo T, Fukuda H, Tachibana H, Yoshida K . Predictive impact of an early change in serum C-reactive protein levels in nivolumab therapy for metastatic renal cell carcinoma. Urol Oncol. 2019; 38(5):526-532. DOI: 10.1016/j.urolonc.2019.12.008. View

17.

Haas M, Lein A, Fuereder T, Schnoell J, Brkic F, Liu D . Early on-treatment C-reactive protein and its kinetics predict survival and response in recurrent and/or metastatic head and neck cancer patients receiving first-line pembrolizumab. Invest New Drugs. 2023; 41(5):727-736. PMC: 10560194. DOI: 10.1007/s10637-023-01388-x. View

18.

Jing S, Afshari K, Guo Z . Inflammatory response-related genes predict prognosis in patients with HNSCC. Immunol Lett. 2023; 259:46-60. DOI: 10.1016/j.imlet.2023.06.003. View

19.

Moutachakkir M, Hanchi A, Baraou A, Boukhira A, Chellak S . Immunoanalytical characteristics of C-reactive protein and high sensitivity C-reactive protein. Ann Biol Clin (Paris). 2017; 75(2):225-229. DOI: 10.1684/abc.2017.1232. View

20.

Hoeh B, Garcia C, Banek S, Klumper N, Cox A, Ellinger J . Early CRP kinetics to predict long-term efficacy of first-line immune-checkpoint inhibition combination therapies in metastatic renal cell carcinoma: an updated multicentre real-world experience applying different CRP kinetics definitions. Clin Transl Immunology. 2023; 12(10):e1471. PMC: 10600333. DOI: 10.1002/cti2.1471. View