Dawn of Staging for Head and Neck Soft Tissue Sarcoma: Validation of the Novel 8th Edition AJCC T Classification and Proposed Stage Groupings

Abstract

After decades of stagnation, the 8th edition TNM (TNM8) introduced a new T classification for head and neck (HN) soft tissue sarcomas (STS). New size cutoffs of 2 and 4 cm define T1-3, and a novel T4 category is defined by local invasion of adjoining structures. These size cutoffs had been chosen arbitrarily to advance data collection in this unique disease site since literature showed approximately 70% of HN STS did not reach the previous size threshold (5 cm) for the existing T1 category. The definition of the TNM8 T categories also align with mucosal HN cancers. No stage grouping for HN STS was defined since this new classification required more data collection to derive stage groups. This study aims to validate the TNM8 T classification and to propose stage groupings. Clinical data of all adult (>16 years) HN STS patients treated from 1988 - 2019 with curative intent in our tertiary cancer center were retrieved from a prospective database, and supplemented with chart review. As per TNM8, cutaneous angiosarcoma, embryonal and alveolar rhabdomyosarcoma, Kaposi sarcoma, and dermatofibrosarcoma protuberans were excluded due to their different behavior. Multivariate analysis (MVA) identified prognostic factors for overall survival (OS). Adjusted hazard ratios (AHR) and recursive partitioning analysis (RPA) were used to derive stage groupings. Stage grouping performance for OS was assessed and also compared against the existing TNM8 groups for non-HN STS. A total of 221 patients (N1: 2; M1: 2) were included. Of the 219 M0 patients, 63% were males; median tumor size was 3.0 cm (range: 0.3-14.0); the proportion of TNM8 T1-T4 were 35%, 34%, 26%, and 5%, respectively. Median follow up was 5.9 years. Five-year OS was 79%. MVA confirmed the prognostic value of T category (T4 HR 7.73, 95% CI 3.62-16.5) and grade (G2/3 vs G1 HR 3.7, 95% CI 1.82-7.53), in addition to age (HR 1.03, 95% CI 1.01-1.04) (all p<0.001) for OS. AHR model derived T1-3_Grade 1 as stage 1; T1-3_Grade 2/3 as stage II; and T4_any Grade or any T_N1 as stage III (Table 1); the corresponding 5-year OS was 93%, 73%, and 38%, respectively. Both patients with M1 died within 1.5 years after diagnosis and M1 disease was designated stage IV. The AHR-grouping outperformed the RPA and non-HN TNM8 stage grouping for hazard consistency, hazard discrimination, percent variance explained, hazard difference, and sample size balance. The novel T4 category introduced in TNM8 is associated with a >7 fold increased risk of death. Grade continues to be a critical prognostic factor in HN STS. The TNM8 HN STS T classifications have been validated, and the proposed new stage groupings with TNM8 incorporating grade have excellent performance for OS.