Neoadjuvant intraarterial cytoreductive chemotherapy for lacrimal gland adenoid cystic carcinoma: A 33-year single-institution experience.

Abstract

e18051 Background: Lacrimal gland adenoid cystic carcinoma (LGACC) has historically been associated with a poor prognosis even in localized disease, with the survival of 56% at 5 years and 49% at 10 years. In 1988, our group treated the first patient with neoadjuvant intra-arterial chemotherapy (IACC) followed by adjuvant chemoradiation. Since then, we use this protocol as the standard approach for localized LGACC. Herein, we aim to analyze the clinical characteristics and outcomes of LGACC patients at a single academic institution treated with the protocol to provide information on this approach's efficacy. Methods: We prospectively assessed all patients with pathologically confirmed LGACC treated at Bascom Palmer, Sylvester Comprehensive Cancer Center, or Jackson Memorial Hospital between 1988 and 2021. We calculated overall survival (OS) using the Kaplan-Meier and Cox proportional-hazards modeling methods with Log-Rank Test to estimate the 95% confidence interval. Results: 42 LGACC patients were identified, and 37 (88%) underwent IACC, with 2 (5%) being metastatic at the time of the protocol. In our cohort, the median follow-up was 10 years, 21 (56%) were men, and the median age at diagnosis was 42 (range 20-72). The average tumor size was 3cm (range 0.8-7.6). The dominant histological pattern was cribriform (n = 23, 54%), followed by basaloid (n = 6, 14%) and solid (n = 6, 14%). 16 patients underwent whole genome sequencing, and the most common mutations found were NOTCH1 (n = 7, 41%), ATM (n = 4, 25%), BPTF (n = 4, 25%), FGFR 2 (n = 3, 18%), Frem3 (n = 3, 18%), and NOTCH2 (n = 3, 18%), with additional biomarker data forthcoming. The 5, and 10-year survival rates were 85% (95% CI 73–97) and 71% (95% CI 53-89), respectively, giving and overall mean survival of 23 years (95% CI 19–28). The risk of death was higher with a tumor size larger than 3 cm and with bone invasion (HR: 6.5 and 7.5 respectively; P < 0.05). Conclusions: Despite the historically described poor prognosis, patients with LGACC treated with IACC have an excellent prognosis. Future research on tumor molecular characteristics might identify susceptibility to targeted therapies such as NOTCH or FGFR inhibitors that could be incorporated into the IACC protocol, further extending its benefits.