707 MITF-mediated changes of tumor architecture, tensile stress and extracellular matrix control intratumor heterogeneity in melanoma

Abstract

Spindle cell melanoma (SCM) is a rare histological subtype of malignant melanoma composed of spindled neoplastic cells. Due to its rarity, population-based clinical and epidemiological characterization is necessary. We searched the National Cancer Database (NCDB) for all cases of SCM confirmed histologically diagnosed from 2004-2016 and excluded those with missing survival information (n¼3906). Kaplan-Meier (KM) and Cox proportional-hazards models were used to analyze the epidemiology and overall survival (OS) of SCM. The median age of diagnosis was 66. Five-year and 10-year OS were 65.0% and 49.6%, respectively. Males represented 64.3% of patients. Head and neck (39.6%) was the most common primary site. Surgery alone (80.2%) was the most common treatment. The mean Breslow thickness was 3.47 mm (SD AE3.00 mm) with 31.1% with ulceration. 79.4% of staged cases presented with American Joint Commission on Cancer (AJCC) Stage I or Stage II disease. 44.4% of cases were treated at academic/research institutions followed by community programs (36.1%) and integrated network cancer programs (INCP) (12.7%). Age (HR¼1.05; CI 95%[1.04-1.06]), black race (HR¼3.0; CI 95%[1.60-5.62]), Breslow thickness greater than 9.8 mm (HR¼1.38; CI 95%[1.04-1.82]), ulceration (HR¼1.51; CI 95%[1.30-1.75]) CDCC score greater than 2 (HR¼2.28; CI 95%[1.72-3.02]), and facility locations in the East South Central (HR¼1.60; CI 95%[1.19-2.15]) and West South Central United States (HR¼1.47; CI 95%[1.06-2.05]) were independently associated with decreased OS. Females (HR¼0.85; CI 95%[0.72-0.99]), primary tumors on the trunk (HR¼0.735; CI 95%[0.61-0.89]) and upper extremities (HR¼0.71; CI 95%[0.55-0.92]), Stage I disease (HR¼0.36; CI 95% [0.13-0.99]), and treatment at INCP (HR¼0.76; CI 95%[0.68-1.42]) are independently associated with increased OS. Our results suggest that when accounting for patient and tumor characteristics, facility type and location significantly impact OS of patients with SCM.