Clinical and genomic characterisation of adenoid cystic carcinoma of the head and neck, lung, and breast.
Authors: Heathcote Emily , Patel Karan , Rack Samuel , Hodgson Clare , Mistry Hitesh , Betts Guy , Bishop Paul , Hall Rachel , Armstrong Anne C. , Harrington Kevin Joseph , Metcalf Robert 
Published: June 2023

6094

Background: Adenoid cystic carcinoma (ACC) arises most commonly within the major salivary glands and other exocrine glands. ACC is typically a slow growing disease with high rates of recurrence many years after diagnosis. To inform post-operative surveillance and to provide comparator data for non-randomised studies, we sought to perform clinical and genomic characterisation of a cohort of 450 ACC patients, comparing outcomes between salivary ACC and other primary sites. Methods: 450 patients with ACC underwent clinical review at 4 UK NHS institutions. Electronic records were reviewed to extract clinical and demographic data. In 225 patients, DNA-based next-generation sequencing was performed to identify alterations in the most frequently altered genes in ACC (NOTCH1, ARID1A, KDM6A, SETD2, or TP53). Kaplan-Meier survival analyses calculated the time to first confirmed recurrence (TTFR) and overall survival from diagnosis (OS-diag) and from first confirmed recurrence (OS-rec). Results: Of 450 ACC patients, the primary site was most frequently the major salivary gland (44.7%; 201/450) comprising parotid (86), submandibular (96), sublingual (9) and salivary NOS (12). Other primary sites were sinonasal (99/450; 22.0%), upper aerodigestive (69/450; 15.3%), tracheobronchial (46/450; 10.2%), breast (16/450; 3.6%), skin (10/450; 2.2%), lacrimal (7/450; 1.6%), and other (2/450; 0.4%). Complete survival data were available in 440 patients. Recurrent/metastatic disease was confirmed in 69.8% (314/450). For these patients, the median TTFR was 4.5 yrs and for those with recurrence, the median OS from recurrence (OS-rec) was 4.8 yrs. The median TTFR in major salivary ACC was 5.8 yrs (95% CI 4.3 – 7.0). In comparison, the shortest median TTFR was seen in tracheobronchial (2.9 yrs, 95% CI 1.6 – 6.8; p = 0.019) and sinonasal ACC (3.8 yrs, 95% CI 2.9 – 5.0; p = 0.004). Breast ACC showed a differing survival pattern compared with major salivary ACC. Although the OS-diag in these two groups was not significantly different (9.75 yrs and 11.3 yrs respectively, p = ns), breast ACC showed a significantly increased TTFR (9.8 versus 4.4 yrs, p = 0.067), and a significantly reduced OS-rec (0.75 versus 4.8 yrs, p = < 0.001). KDM6A mutation was seen more frequently in primary sites outside the major salivary glands (p = 0.005). However, there was no relationship between primary tumour site and mutations in NOTCH1, ARID1A, SETD2 or TP53. Conclusions: In this real-world multi-centre UK study, tracheobronchial and sinonasal ACC have significantly shorter TTFR than major salivary ACC. This study suggests that breast ACC has a similar OS from diagnosis to major salivary ACC, but has an increased TTFR and shorter OS following recurrence. This may have implications for follow-up protocols after primary treatment of breast ACC, and initiation of systemic therapy following recurrence.