Background: Cutaneous squamous cell carcinoma of the head and neck (cSCCHN) in the setting of chronic immunosuppression (IS) is notoriously aggressive. Defining the outcomes of cSCCHN in immunosuppressed patients is essential to better risk stratify and optimize treatment.
Objective: To characterize and determine prognostic factors influencing overall survival in cSCCHN patients with IS compared to those with no chronic immunosuppression (nIS).
Methods: Retrospective review of 972 consecutive patients with cSCCHN regardless of prior treatment treated at the University of Texas MD Anderson Cancer Center between 1996 and 2014 was undertaken. The primary outcome measure was overall survival (OS). Secondary outcomes were disease specific survival (DSS) and locoregional recurrence rate (LRR). Univariate and multivariate analyses were undertaken using the Cox proportional hazards regression model. Recursive partitioning analysis was used to risk stratify patients with CI according to OS.
Results: Of 972 cSCCHN patients included, 189 (19.4%) were characterized as IS. The most common causes of IS were insulin dependent diabetes mellitus (n=96, 50.8%), hematologic malignancy (n=51, 27.0%), and organ transplantation (n=35, 18.5%). At the time of presentation, there was no significant difference between IS and nIS patients in the TNM classification or overall stage (AJCC 7).
Five-year OS was significantly worse in patients with IS (31.6%, 95% confidence interval [CI]=23.8-39.8%) compared to nIS patients (53.1%, 95% CI=48.9-57.1%; p<0.001). Five-year DSS was 59.1% (95% CI=48.9-67.9%) in patients with IS compared to 78.8% (95% CI=75.0-82.1%) in nIS patients (p<0.001). Five-year LRR was not different in patients with chronic IS (74.9%, 95% CI=64.8-82.5%) compared to nIS patients (82.1%, 95% CI=78.4-85.3%, p=0.186). Using multivariate analysis, IS was found to be an independent predictor of OS (hazard ratio [HR] = 1.63, 95% CI=1.31-2.03) and DSS (HR=2.26, 95% CI=1.64-3.11).
Recursive partitioning analysis stratified cSCCHN patients with chronic IS into 4 groups: 1) those without prior radiotherapy and chronic IS due to insulin-dependent diabetes, autoimmune disease requiring treatment, organ or stem cell transplantation, or autoimmune deficiency syndrome (AIDS); 2) those without prior radiotherapy and chronic immunosuppression due to hematologic malignancy or other reasons (HR=1.53, 0.99-2.35); 3) those with prior radiotherapy and presenting with no nodal disease (HR=2.05, 95% CI=1.18-3.55), and 4) those with prior radiotherapy and presenting with nodal disease (HR=6.2, 95% CI=3.14-12.10).
Conclusion and Relevance: Chronic immunosuppression (IS) is an independent predictor of worse overall and disease-specific survival in patient presenting with cSCCHN. Prior treatment with radiotherapy was the most important prognostic factor in these patients, followed by reason for IS and presence of nodal disease. Risk stratification may allow for improved patient counselling, prognostication, and treatment decision-making in chronically immunosuppressed patients with cSCCHN.