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C-Reactive Protein-to-Albumin Ratio as Prognostic Marker for Anal Squamous Cell Carcinoma Treated With Chemoradiotherapy


C-Reactive Protein-to-Albumin Ratio as Prognostic Marker for Anal Squamous Cell Carcinoma Treated With Chemoradiotherapy

Daniel Martin et al. Front Oncol.


Background: Definitive chemoradiotherapy (CRT) is the primary treatment for non-metastatic anal squamous cell carcinoma (ASCC). Despite favorable treatment outcomes in general, failure rates up to 40% occur in locally advanced disease. For treatment escalation or de-escalation strategies easily assessable and valid biomarkers are needed. Methods: We identified 125 patients with ASCC treated with standard CRT at our department. C-reactive protein (CRP) to albumin ratio (CAR) was calculated dividing baseline CRP by baseline albumin levels. We used maximally selected rank statistics to dichotomize patients to high and low risk groups. Associations of CAR with clinicopathologic parameters were evaluated and the prognostic impact was tested using univariate and multivariate cox regression analysis. In a subset of 78 patients, pretreatment tumor tissue was available and CD8+ tumor infiltrating lymphocytes (TILs) and p16INK4a status were scored by immunohistochemistry and correlated with CAR. Results: Advanced T-stage and male gender were significantly associated with higher baseline CAR. Using the calculated cutoff of 0.117, a high baseline CAR was also associated with worse locoregional control (p = 0.002), distant metastasis-free survival (p = 0.01), disease-free survival (DFS, p = 0.002) and overall survival (OS, p < 0.001). A combined risk score incorporating N-stage and CAR, termed N-CAR score, was associated with worse outcome across all endpoints and in multivariate analysis independent of T-stage and Gender (HR 4.27, p = 0.003). In the subset of 78 patients, a strong infiltration with intratumoral CD8+ TIL was associated with a significantly lower CAR (p = 0.007). CAR is an easily accessible biomarker that is associated with DFS. Our study revealed a possible link between chronic systemic inflammation and an impaired intratumoral immune response.

Keywords: C-reactive protein; albumin; anal cancer; biomarker; disease-free survival.


Figure 1
Figure 1
Patients with advanced T-stage and male gender had a significantly elevated CAR before initiation of treatment (A). Patients with high baseline CAR had a worse LRC (B), DFS (C), and OS (D). CAR, CRP-albumin-ratio; LRC, locoregional control; DFS, disease-free survival; OS, overall survival.
Figure 2
Figure 2
A combined score of N-stage and CAR was associated with worse LRC (A), DFS (B), and OS (C). Forest plot showing that N-CAR remained a significant prognostic factor for DFS in a multivariate cox regression analysis with gender and T-stage (D). CAR, CRP-albumin-ratio; LRC, locoregional control; DFS, disease-free survival.
Figure 3
Figure 3
Strong intratumoral infiltration with CD8+ TIL was associated with elevated CAR at baseline, whereas there was no association between peritumoral TIL and CAR (A). Exemplary stainings for high and low intratumoral and peritumoral infiltrations with CD8+ TIL (B). Forest plot of a multivariate cox regression model including CAR and CD8 TIL (C) and CAR and p16 (D) for DFS. CAR, CRP-albumin-ratio; TIL, tumor-infiltrating-lymphocyte.

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    1. Bouvier A-M, Belot A, Manfredi S, Jooste V, Uhry Z, Faivre J, et al. . Trends of incidence and survival in squamous-cell carcinoma of the anal canal in France: a population-based study. Eur J Cancer Prev. (2016) 25:182–7. 10.1097/CEJ.0000000000000163 - DOI - PubMed
    1. Guren MG, Aagnes B, Nygård M, Dahl O, Møller B. Rising incidence and improved survival of anal squamous cell carcinoma in Norway, 1987-2016. Clin Colorectal Cancer. (2018) 18:e96–103. 10.1016/j.clcc.2018.10.001 - DOI - PubMed
    1. James RD, Glynne-Jones R, Meadows HM, Cunningham D, Myint AS, Saunders MP, et al. . Mitomycin or cisplatin chemoradiation with or without maintenance chemotherapy for treatment of squamous-cell carcinoma of the anus (ACT II): a randomised, phase 3, open-label, 2 × 2 factorial trial. Lancet Oncol. (2013) 14:516–24. 10.1016/S1470-2045(13)70086-X - DOI - PubMed
    1. Gunderson LL, Winter KA, Ajani JA, Pedersen JE, Moughan J, Benson AB, et al. . Long-term update of US GI intergroup RTOG 98-11 phase III trial for anal carcinoma: survival, relapse, and colostomy failure with concurrent chemoradiation involving fluorouracil/mitomycin versus fluorouracil/cisplatin. J Clin Oncol. (2012) 30:4344–51. 10.1200/JCO.2012.43.8085 - DOI - PMC - PubMed
    1. Pan YB, Maeda Y, Wilson A, Glynne-Jones R, Vaizey CJ. Late gastrointestinal toxicity after radiotherapy for anal cancer: a systematic literature review. Acta Oncol. (2018) 57:1427–37. 10.1080/0284186X.2018.1503713 - DOI - PubMed