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

Abstract

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.

The Influence of Systemic Inflammation on Treatment Response and Survival in Anal Squamous Cell Cancer

“…The NLR was not significantly associated with overall survival on univariate analysis using a threshold of 3 (HR 1.66, 95% CI 0.81-3. 41 prognostic of inferior cancer-specific survival, independent of TNM stage (HR 5.00, 95% CI 1.82 -13.69, p=0.002). There were no significant relationships between NLR and overall or cancer-specific survival on univariate analysis, regardless of threshold value used.…”

Predictive impact of C-reactive protein to albumin ratio for recurrent or metastatic head and neck squamous cell carcinoma receiving nivolumab

“…There is no consensus about the CAR cutoff for ICI-treated patients. Although the importance of CAR as a prognostic factor has already been reported in other squamous cell carcinoma (SCC) such as anal squamous cell carcinoma 24 and esophageal cancer 25 , the proposed cutoff values vary in the several literatures. The major possible reasons would be the differences in the calculating method or patient background such as disease stage or cancer type and indeed, a positive correlation between disease stage and CAR has been reported in SCC 22 , 24 .…”

“…Although the importance of CAR as a prognostic factor has already been reported in other squamous cell carcinoma (SCC) such as anal squamous cell carcinoma 24 and esophageal cancer 25 , the proposed cutoff values vary in the several literatures. The major possible reasons would be the differences in the calculating method or patient background such as disease stage or cancer type and indeed, a positive correlation between disease stage and CAR has been reported in SCC 22 , 24 . While for preoperative head and neck cancer, the cutoff of CAR was set at 0.32 18 , it was set at 0.189 for cisplatin-based treated patients with metastatic nasopharyngeal carcinoma 26 .…”

“…On the other hand, no significant change of systemic levels of IL-6 during ICI treatment has been observed in the studies of melanoma 38 and gastric cancer 39 . In addition, several reports have already shown that CAR is an important prognostic factor for SCC treated with chemoradiotherapy 24 or cytotoxic agents 26 . Therefore, CAR might not necessarily be an ICI-specific predictor, but a powerful prognosis factor for various types of cancer under different conditions.…”

Preoperative plus postoperative neutrophil‑lymphocyte ratio for predicting overall survival following partial hepatectomy for hepatocellular carcinoma

“…The optimal cut-off for continuous variables was determined by using the maximally selected rank statistics by the ‘surv_cutpoint’ function of the ‘survminer’ R package ( 26 , 27 ). The time-dependent receiver operating characteristic (td-ROC) curve was estimated to assess the performance of the preoperative NLR, postoperative NLR, postoperative NLR change, preoperative NLR plus postoperative NLR, and postoperative NLR minus preoperative NLR.…”