Long term clinical outcomes and associated predictors of progression free survival in anal canal cancer.

Background: Reports of long term clinical outcomes for patients with squamous cell carcinoma (SCC) of the anal canal treated with chemotherapy and intensity modulated radiation therapy (IMRT) are limited. Pre-treatment hematologic variables associated with outcomes remain understudied. We sought to report the long-term clinical outcomes of a cohort of patients treated with definitive chemoradiation (CRT) utilizing helical tomotherapy (HT) IMRT at a single tertiary referral center. We further sought to examine for any correlations between pre-treatment hematologic parameters and progression free survival (PFS).

Methods: Data from patients with SCC of the anal canal treated with definitive CRT using HT IMRT from 2005 to 2017 were collected. Pre-treatment patient characteristics examined for correlations with PFS included: hemoglobin (Hgb) level, age, diabetes mellitus (DM) status, smoking status, neutropenia, thrombocytopenia, leukopenia, neutrophil/lymphocyte ratio, neutrophil/WBC ratio, lymphocyte/WBC ratio, sex, transplant status, HIV status, Karnofsky performance score, T-stage, and N-stage. Pre-treatment Hgb levels were recorded within two weeks prior to starting CRT. Clinical outcomes, including PFS, were described using the Kaplan-Meier estimator. A multivariable (MVA) Cox model of PFS evaluated the impact of pre-treatment Hgb and diabetes while adjusting for T-stage and age.

Results: The median patient age was 57 years old (range, 26-87) and there were 39 females (63.9%) with the remaining patients identifying as males. Median patient follow up was 5.8 years. The PFS was 83% at 5 years. The median pre-treatment Hgb was 13 g/dL. On multivariable analysis (MVA), Hgb ≤10 g/dL (HR: 11.891, 95% CI: 2.649-53.391, P=0.001) and a diagnosis of diabetes mellitus (HR: 4.524, 95% CI: 1.436-14.252, P=0.010) were both significantly associated with a worse PFS. These factors were independent of T-stage and age.

Conclusions: Long-term clinical outcomes for patients with SCC of the anal canal treated with definitive CRT are presented. Pre-treatment hemoglobin of ≤10 g/dL and diabetes were both independently associated with worse PFS on MVA. This retrospective data supports further prospective study of the impact of hematologic markers and medical co-morbidities such as DM and their management on clinical outcomes for patients with SCC of the anal canal treated with curative-intent CRT.