THE IMPACT OF ANEMIA ON TREATMENT OUTCOME IN PATIENTS WITH SQUAMOUS CELL CARCINOMA OF ANAL CANAL AND ANAL MARGIN

Abstract

BACKGROUND AND PURPOSE: Radiochemotherapy (RCT) is the main therapy for patients with squamous cell carcinoma of the anal canal. Anemia with poor oxygen delivery to the tumor cells can be one of the factors with negative impact on the treatment outcome. Our study aimed to evaluate the impact of pre-treatment, mean on-treatment and end-of-treatment hemoglobin (Hb) on the clinical outcome of patients with anal canal cancer.

PATIENTS AND METHODS: This is a retrospective study of 100 patients with histologically confirmed squamous cell carcinoma of the anal canal treated with radical RCT at the Institute of Oncology Ljubljana from January 2003 till June 2013. The treatment consisted of 3-dimensional (3-D) conformal radiation therapy or intensity-modulated radiation therapy (IMRT) with concurrent chemotherapy (CT) (fluoropyrimidine derivatives and Mitomycin C (MMC)) followed by additional brachytherapy (BT) or external beam radiotherapy (RT) boost. The patients were clinically examined on weekly basis and the potential side effects were documented, as well as blood tests were done. SPSS software package was used to analyze the prognostic value of pre-treatment, mean on-treatment and end-of-treatment Hb. We used the Kaplan-Meier method in the univariate analysis of survival, and the log-rank test to determine the differences between the groups of patients. Independent significant prognostic factors were identified with the multivariate Cox regression analysis. Two-sided statistical tests were used. Differences at P<0.05 were marked as statistically significant.

RESULTS: The treatment was completed according to the protocol in 92 % of patients. The pre-treatment Hb level of >120 g/L was associated with a statistically significant better tumor response (P=0.031), while mean on-treatment Hb level and end-of-treatment Hb level of >120 g/L showed no statistically significant effect. The pre-treatment Hb level of >120 g/L was a prognostic factor for statistically significant better loco-regional control (LRC) (P=0.011), disease-free survival (DFS) (P=0.017), disease-specific survival (DSS) (P=0.003) and overall survival (OS) (P<0.0001). The end-of-treatment Hb level of >120 g/L was also a statistically significant prognostic factor for better LRC (P=0.022), DFS (P=0.037), DSS (P=0.011) and OS (P=0.003). The mean on-treatment Hb level of >120 g/L, however, was a statistically significant prognostic factor for better LRC (P=0.037) and OS (P=0.007), but not for better DSS (P=0.081), while the effect on better DFS was on the border of statistical significance (P=0.054). In the multivariate analysis, overall stage (P=0.015) and pre-treatment Hb (P=0.032) were identified as independent prognostic factors for OS. Also, overall stage was an independent prognostic factor for DSS (P=0,009). The 5-year LRC, DFS, DSS and OS rates were 72%, 71%, 77% and 62%, respectively.

CONCLUSIONS: Anemic patients with squamous cell carcinoma of the anal canal were shown to have worse clinical outcome after the treatment with RCT. Pre-treatment, mean on-treatment and end-of-treatment Hb levels had all statistically significant impact on the treatment outcome. However, the most important is pre-treatment Hb, as it is proved to be an independent prognostic factor for OS of patients with anal canal cancer.

KEY WORDS: Anemia, Anal canal squamous cell carcinoma, Radiochemotherapy, Outcome